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Exercise, Learned Helplessness, and the Stress-Resistant Brain

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Abstract

Exercise can prevent the development of stress-related mood disorders, such as depression and anxiety. The underlying neurobiological mechanisms of this effect, however, remain unknown. Recently, researchers have used animal models to begin to elucidate the potential mechanisms underlying the protective effects of physical activity. Using the behavioral consequences of uncontrollable stress or “learned helplessness” as an animal analog of depression- and anxiety-like behaviors in rats, we are investigating factors that could be important for the antidepressant and anxiolytic properties of exercise (i.e., wheel running). The current review focuses on the following: (1) the effect of exercise on the behavioral consequences of uncontrollable stress and the implications of these effects on the specificity of the “learned helplessness” animal model; (2) the neurocircuitry of learned helplessness and the role of serotonin; and (3) exercise-associated neural adaptations and neural plasticity that may contribute to the stress-resistant brain. Identifying the mechanisms by which exercise prevents learned helplessness could shed light on the complex neurobiology of depression and anxiety and potentially lead to novel strategies for the prevention of stress-related mood disorders.

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References

  • Abrams, J. K., Johnson, P. L., Hay-Schmidt, A., et al. (2005). Serotonergic systems associated with arousal and vigilance behaviors following administration of anxiogenic drugs. Neuroscience, 133, 983–997.

    PubMed  CAS  Google Scholar 

  • Abrams, J. K., Johnson, P. L., Hollis, J. H., et al. (2004). Anatomic and functional topography of the dorsal raphe nucleus. Annals of the New York Academy of Sciences, 1018, 46–57.

    PubMed  Google Scholar 

  • Adell, A., Celada, P., & Artigas, F. (2001). The role of 5-HT1B receptors in the regulation of serotonin cell firing and release in the rat brain. Journal of Neurochemistry, 79, 172–182.

    PubMed  CAS  Google Scholar 

  • Adlard, P. A., & Cotman, C. W. (2004). Voluntary exercise protects against stress-induced decreases in brain-derived neurotrophic factor protein expression. Neuroscience, 124, 985–992.

    PubMed  CAS  Google Scholar 

  • Aghajanian, G. K. (1985). Modulation of a transient outward current in serotonergic neurones by alpha 1-adrenoceptors. Nature, 315, 501–503.

    PubMed  CAS  Google Scholar 

  • Amat, J., Baratta, M. V., Paul, E., et al. (2005). Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus. Nature Neuroscience, 8, 365–371.

    PubMed  CAS  Google Scholar 

  • Amat, J., Matus-Amat, P., Watkins, L. R., et al. (1998a). Escapable and inescapable stress differentially alter extracellular levels of 5-HT in the basolateral amygdala of the rat. Brain Research, 812, 113–120.

    PubMed  CAS  Google Scholar 

  • Amat, J., Matus-Amat, P., Watkins, L. R., et al. (1998b). Escapable and inescapable stress differentially and selectively alter extracellular levels of 5-HT in the ventral hippocampus and dorsal periaqueductal gray of the rat. Brain Research, 797, 12–22.

    PubMed  CAS  Google Scholar 

  • Amat, J., Paul, E., Zarza, C., et al. (2006). Previous experience with behavioral control over stress blocks the behavioral and dorsal raphe nucleus activating effects of later uncontrollable stress: Role of the ventral medial prefrontal cortex. Journal of Neuroscience, 26, 13264–13272.

    PubMed  CAS  Google Scholar 

  • Amat, J., Sparks, P. D., Matus-Amat, P., et al. (2001). The role of the habenular complex in the elevation of dorsal raphe nucleus serotonin and the changes in the behavioral responses produced by uncontrollable stress. Brain Research, 917, 118–126.

    PubMed  CAS  Google Scholar 

  • Anderson, I. M., & Mortimore, C. (1999). 5-HT and human anxiety. Evidence from studies using acute tryptophan depletion. Advances in Experimental Medicine and Biology, 467, 43–55.

    PubMed  CAS  Google Scholar 

  • Babyak, M., Blumenthal, J. A., Herman, S. P., et al. (2000). Exercise treatment for major depression: Maintenance of therapeutic benefit at 10 months. Psychosomatic Medicine, 62, 633–638.

    PubMed  CAS  Google Scholar 

  • Bailey, S. P., Davis, J. M., & Ahlborn, E. N. (1992). Effect of increased brain serotonergic activity on endurance performance in the rat. Acta Physiologica Scandinavica, 145, 75–76.

    Article  PubMed  CAS  Google Scholar 

  • Bailey, S. P., Davis, J. M., & Ahlborn, E. N. (1993). Serotonergic agonists and antagonists affect endurance performance in the rat. International Journal of Sports Medicine, 14, 330–333.

    PubMed  CAS  Google Scholar 

  • Baker, S. C., Frith, C. D., & Dolan, R. J. (1997). The interaction between mood and cognitive function studied with PET. Psychological Medicine, 27, 565–578.

    PubMed  CAS  Google Scholar 

  • Barde, Y. A. (1994). Neurotrophins: A family of proteins supporting the survival of neurons. Progress in Clinical and Biological Research, 390, 45–56.

    PubMed  CAS  Google Scholar 

  • Beasley, C. M. Jr., & Potvin, J. H. (1993). Fluoxetine: Activating and sedating effects. International Clinical Psychopharmacology, 8, 271–275.

    Article  PubMed  Google Scholar 

  • Bequet, F., Gomez-Merino, D., Berthelot, M., et al. (2001). Exercise-induced changes in brain glucose and serotonin revealed by microdialysis in rat hippocampus: Effect of glucose supplementation. Acta Physiologica Scandinavica, 173, 223–230.

    PubMed  CAS  Google Scholar 

  • Binder, E., Droste, S. K., Ohl, F., et al. (2004). Regular voluntary exercise reduces anxiety-related behaviour and impulsiveness in mice. Behavioural Brain Research, 155, 197–206.

    PubMed  Google Scholar 

  • Bjornebekk, A., Mathe, A. A., & Brene, S. (2005). The antidepressant effect of running is associated with increased hippocampal cell proliferation. International Journal of Neuropsychopharmacology, 8, 357–368.

    PubMed  CAS  Google Scholar 

  • Bjornebekk, A., Mathe, A. A., & Brene, S. (2006). Running has differential effects on NPY, opiates, and cell proliferation in an animal model of depression and controls. Neuropsychopharmacology, 31, 256–264.

    PubMed  CAS  Google Scholar 

  • Bland, S. T., Tamlyn, J. P., Barrientos, R. M., et al. (2007). Expression of fibroblast growth factor-2 and brain-derived neurotrophic factor mRNA in the medial prefrontal cortex and hippocampus after uncontrollable or controllable stress. Neuroscience, 144, 1219–1228.

    PubMed  CAS  Google Scholar 

  • Blomstrand, E., Perrett, D., Parry-Billings, M., et al. (1989). Effect of sustained exercise on plasma amino acid concentrations and on 5-hydroxytryptamine metabolism in six different brain regions in the rat Acta Physiologica Scandinavica, 136, 473–481.

    PubMed  CAS  Google Scholar 

  • Blumenthal, J. A., Babyak, M. A., Moore, K. A., et al. (1999). Effects of exercise training on older patients with major depression. Archives of Internal Medicine, 159, 2349–2356.

    PubMed  CAS  Google Scholar 

  • Bremner, J. D., Staib, L. H., Kaloupek, D., et al. (1999). Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: A positron emission tomography study. Biological Psychiatry, 45, 806–816.

    PubMed  CAS  Google Scholar 

  • Brosse, A. L., Sheets, E. S., Lett, H. S., et al. (2002). Exercise and the treatment of clinical depression in adults: Recent findings and future directions. Sports Medicine, 32, 741–760.

    PubMed  Google Scholar 

  • Brown, L., Rosellini, R. A., Samuels, O. B., et al. (1982). Evidence for a serotonergic mechanism of the learned helplessness phenomenon. Pharmacology Biochemistry and Behavior, 17, 877–883.

    CAS  Google Scholar 

  • Burghardt, P. R., Fulk, L. J., Hand, G. A., et al. (2004). The effects of chronic treadmill and wheel running on behavior in rats. Brain Research, 1019, 84–96.

    PubMed  CAS  Google Scholar 

  • Burghardt, P. R., Pasumarthi, R. K., Wilson, M. A., et al. (2006). Alterations in fear conditioning and amygdalar activation following chronic wheel running in rats. Pharmacology Biochemistry and Behavior, 84, 306–312.

    CAS  Google Scholar 

  • Campisi, J., Leem, T. H., Greenwood, B. N., et al. (2003). Habitual physical activity facilitates stress-induced HSP72 induction in brain, peripheral, and immune tissues. American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 284, R520–R530.

    CAS  Google Scholar 

  • Chambliss, H. O., Van Hoomissen, J. D., & Holmes, P. V. (2004). Effects of chronic activity wheel running and imipramine on masculine copulatory behavior after olfactory bulbectomy. Physiology & Behavior, 82, 593–600.

    CAS  Google Scholar 

  • Chaouloff, F. (1994). Influence of physical exercise on 5-HT1A receptor- and anxiety-related behaviours. Neuroscience Letters, 176, 226–230.

    PubMed  CAS  Google Scholar 

  • Clark, M. S., McDevitt, R. A., & Neumaier, J. F. (2006). Quantitative mapping of tryptophan hydroxylase-2, 5-HT1A, 5-HT1B, and serotonin transporter expression across the anteroposterior axis of the rat dorsal and median raphe nuclei. Journal of Comparative Neurology, 498, 611–623.

    PubMed  CAS  Google Scholar 

  • Colcombe, S. J., Erickson, K. I., Scalf, P. E., et al. (2006). Aerobic exercise training increases brain volume in aging humans. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 61(11), 1166–1170.

    Google Scholar 

  • Coppen, A. J., & Doogan, D. P. (1988). Serotonin and its place in the pathogenesis of depression. Journal of Clinical Psychiatry, 49(Suppl), 4–11.

    PubMed  Google Scholar 

  • Cotman, C. W., & Engesser-Cesar, C. (2002). Exercise enhances and protects brain function. Exercise and Sport Sciences Reviews, 30, 75–79.

    PubMed  Google Scholar 

  • Cusin, C., Fava, M., Amsterdam, J. D., et al. (2007). Early symptomatic worsening during treatment with fluoxetine in major depressive disorder: Prevalence and implications. Journal of Clinical Psychiatry, 68, 52–57.

    Article  PubMed  CAS  Google Scholar 

  • Czeh, B., Müller-Keuker, J. I., Rygula, R., et al. (2006). Chronic social stress inhibits cell proliferation in the adult medial prefrontal cortex: Hemispheric asymmetry and reversal by fluoxetine treatment. Neuropsychopharmacology, 32, 1490–1503.

    PubMed  Google Scholar 

  • Davis, J. M., & Bailey, S. P. (1997). Possible mechanisms of central nervous system fatigue during exercise. Medicine and Science in Sports and Exercise, 29, 45–57.

    PubMed  CAS  Google Scholar 

  • Day, H. E., Greenwood, B. N., Hammack, S. E., et al. (2004). Differential expression of 5HT-1A, alpha1b adrenergic, CRF-R1, and CRF-R2 receptor mRNA in serotonergic, gamma-aminobutyric acidergic, and catecholaminergic cells of the rat dorsal raphe nucleus. Journal of Comparative Neurology, 474, 364–78.

    PubMed  CAS  Google Scholar 

  • Day, H. E., Wolf, E. M., Herlihy, L., Campeau, S. (2006). The effect of voluntary exercise on the acute HPA axis response to mild stress in rats. Neuroscience Meeting Planner. Atlanta, GA: Society for Neuroscience Online, Program No. 563.20.

  • Delgado, P. L., Miller, H. L., Salomon, R. M., et al. (1999). Tryptophan-depletion challenge in depressed patients treated with desipramine or fluoxetine: Implications for the role of serotonin in the mechanism of antidepressant action. Biological Psychiatry, 46, 212–220.

    PubMed  CAS  Google Scholar 

  • Dietrich, A. (2006). Transient hypofrontality as a mechanism for the psychological effects of exercise. Psychiatry Research, 145, 79–83.

    PubMed  Google Scholar 

  • Dishman, R. K. (1997). The norepinephrine hypothesis. In W. P. Morgan (Ed.), Physical activity and mental health. Washington, DC: Taylor & Francis.

    Google Scholar 

  • Dishman, R. K., Berthoud, H.-R., Booth, F. W., et al. (2006). Neurobiology of exercise. Obesity (Silver Spring), 14, 345–356.

    CAS  Google Scholar 

  • Dishman, R. K., Renner, K. J., Youngstedt, S. D., et al. (1997a). Activity wheel running reduces escape latency and alters brain monoamine levels after footshock. Brain Research Bulletin, 42, 399–406.

    PubMed  CAS  Google Scholar 

  • Dishman, R. K., Warren, J. M., & Hong, S. (2000). Treadmill exercise training blunts suppression of splenic natural killer cell cytolysis after footshock. Journal of Applied Physiology, 88, 2176–2182.

    PubMed  CAS  Google Scholar 

  • Dishman, R. K., Warren, J. M., Youngstedt, S. D., et al. (1997b). Brain monoamines, exercise, and behavioral stress: Animal models. Medicine and Science in Sports and Exercise, 29, 63–74.

    PubMed  CAS  Google Scholar 

  • Dong, H. W., Petrovich, G. D., Watts, A. G., et al. (2001). Basic organization of projections from the oval and fusiform nuclei of the bed nuclei of the stria terminalis in adult rat brain. Journal of Comparative Neurology, 436, 430–455.

    PubMed  CAS  Google Scholar 

  • Drevets, W. C. (2000). Functional anatomical abnormalities in limbic and prefrontal cortical structures in major depression. Prog Brain Res., 126, 413–431.

    PubMed  CAS  Google Scholar 

  • Droste, S. K., Chandramohan, Y., Hill, L. E., et al. (2007). Voluntary exercise impacts on the rat hypothalamic–pituitary–adrenocortical axis mainly at the adrenal level. Neuroendocrinology, 86, 26–37.

    PubMed  CAS  Google Scholar 

  • Droste, S. K., Gesing, A., Ulbricht, S., et al. (2003). Effects of long-term voluntary exercise on the mouse hypothalamic–pituitary–adrenocortical axis. Endocrinology, 144, 3012–3023.

    PubMed  CAS  Google Scholar 

  • Droste, S. K., Schweizer, M. C., Ulbricht, S., et al. (2006). Long-term voluntary exercise and the mouse hypothalamic–pituitary–adrenocortical axis: Impact of concurrent treatment with the antidepressant drug tianeptine. Journal of Neuroendocrinology, 18, 915–925.

    PubMed  CAS  Google Scholar 

  • Drugan, R. C., Ryan, S. M., Minor, T. R., et al. (1984). Librium prevents the analgesia and shuttlebox escape deficit typically observed following inescapable shock. Pharmacology Biochemistry and Behavior, 21, 749–754.

    CAS  Google Scholar 

  • Duman, R. S. (2004). Role of neurotrophic factors in the etiology and treatment of mood disorders. Neuromolecular Medicine, 5, 11–25.

    PubMed  CAS  Google Scholar 

  • Duman, R. S. (2005). Neurotrophic factors and regulation of mood: Role of exercise, diet and metabolism. Neurobiology of Aging, 26(Suppl 1), 88–93.

    PubMed  Google Scholar 

  • Duman, R. S., Heninger, G. R., & Nestler, E. J. (1997). A molecular and cellular theory of depression. Archives of General Psychiatry, 54, 597–606.

    PubMed  CAS  Google Scholar 

  • Duman, R. S., & Monteggia, L. M. (2006). A neurotrophic model for stress-related mood disorders. Biological Psychiatry, 59, 1116–1127.

    PubMed  CAS  Google Scholar 

  • Dunn, A. L., & Dishman, R. K. (1991). Exercise and the neurobiology of depression. Exercise and Sport Sciences Reviews, 19, 41–98.

    PubMed  CAS  Google Scholar 

  • Dunn, A. L., Reigle, T. G., & Youngstedt, S. D. (1996). Brain monoamines and metabolites after treadmill training and wheel running in rats. Medicine and Science in Sports and Exercise, 28, 204–209.

    PubMed  CAS  Google Scholar 

  • Dunn, A. L., Trivedi, M. H., & O’Neal, H. A. (2001). Physical activity dose–response effects on outcomes of depression and anxiety. Medicine and Science in Sports and Exercise, 33(6 Suppl), S587–S597.

    PubMed  CAS  Google Scholar 

  • Figueiredo, H. F., Bruestle, A., Bodie, B., Dolgas, C. M., & Herman, J. P. (2003). The medial prefrontal cortex differentially regulates stress-induced c-fos expression in the forebrain depending on type of stressor. European Journal of Neuroscience, 18, 2357–2364.

    PubMed  Google Scholar 

  • Fleshner, M. (2000). Exercise and neuroendocrine regulation of antibody production: Protective effect of physical activity on stress-induced suppression of the specific antibody response. International Journal of Sports Medicine, 21(Suppl 1), S14–S19.

    PubMed  CAS  Google Scholar 

  • Foley, T. E., Greenwood, B. N., Day, H. E., et al. (2006). Elevated central monoamine receptor mRNA in rats bred for high endurance capacity: Implications for central fatigue. Behavioural Brain Research, 174, 132–42.

    PubMed  CAS  Google Scholar 

  • Fox, K. R. (1999). The influence of physical activity on mental well-being. Public Health Nutrition, 2, 411–418.

    PubMed  CAS  Google Scholar 

  • Gerrits, M., Westenbroek, C., Fokkema, D. S., et al. (2003). Increased stress vulnerability after a prefrontal cortex lesion in female rats. Brain Research Bulletin, 61, 627–635.

    PubMed  Google Scholar 

  • Gold, P. W., & Chrousos, G. P. (1999). The endocrinology of melancholic and atypical depression: Relation to neurocircuitry and somatic consequences. Proceedings of the Association of American Physicians, 111, 22–34.

    PubMed  CAS  Google Scholar 

  • Gomez-Merino, D., Béquet, F., Berthelot, M., et al. (2001). Site-dependent effects of an acute intensive exercise on extracellular 5-HT and 5-HIAA levels in rat brain. Neuroscience Letters, 301, 143–146.

    PubMed  CAS  Google Scholar 

  • Gomez-Pinilla, F., So, V., & Kesslak, J. P. (1998). Spatial learning and physical activity contribute to the induction of fibroblast growth factor: Neural substrates for increased cognition associated with exercise. Neuroscience, 85, 53–61.

    PubMed  CAS  Google Scholar 

  • Gorman, J. M. (1996). Comorbid depression and anxiety spectrum disorders. Depress and Anxiety, 4, 160–168.

    Google Scholar 

  • Graeff, F. G., Guimarães, F. S., De Andrade, T. G., et al. (1996). Role of 5-HT in stress, anxiety, and depression. Pharmacology Biochemistry and Behavior, 54, 129–141.

    CAS  Google Scholar 

  • Graeff, F. G., Silveira, M. C., Nogueira, R. L., et al. (1993). Role of the amygdala and periaqueductal gray in anxiety and panic. Behavioural Brain Research, 58, 123–131.

    PubMed  CAS  Google Scholar 

  • Graeff, F. G., Viana, M. B., & Mora, P. O. (1997). Dual role of 5-HT in defense and anxiety. Neuroscience and Biobehavioral Reviews, 21, 791–799.

    PubMed  CAS  Google Scholar 

  • Grahn, R., Hammack, S. E., Will, M. J., et al. (2002). Blockade of alpha1 adrenoreceptors in the dorsal raphe nucleus prevents enhanced conditioned fear and impaired escape performance following uncontrollable stressor exposure in rats. Behavioural Brain Research, 134, 387–392.

    PubMed  CAS  Google Scholar 

  • Grahn, R. E., Will, M. J., Hammack, S. E., et al. (1999). Activation of serotonin-immunoreactive cells in the dorsal raphe nucleus in rats exposed to an uncontrollable stressor. Brain Research, 826, 35–43.

    PubMed  CAS  Google Scholar 

  • Grant, M. M., & Weiss, J. M. (2001). Effects of chronic antidepressant drug administration and electroconvulsive shock on locus coeruleus electrophysiologic activity. Biological Psychiatry, 49, 117–129.

    PubMed  CAS  Google Scholar 

  • Greenwood, B. N., Foley, T. E., Burhans, D., et al. (2005a). The consequences of uncontrollable stress are sensitive to duration of prior wheel running. Brain Research, 1033, 164–178.

    PubMed  CAS  Google Scholar 

  • Greenwood, B. N., Foley, T., Day, H., et al. (2005b). Wheel running alters serotonin (5-HT) transporter, 5-HT(1A), 5-HT(1B), and alpha(1b)-adrenergic receptor mRNA in the rat raphe nuclei. Biological Psychiatry, 57, 559–568.

    PubMed  CAS  Google Scholar 

  • Greenwood, B. N., Foley, T. E., Day, H. E., et al. (2003a). Freewheel running prevents learned helplessness/behavioral depression: Role of dorsal raphe serotonergic neurons. Journal of Neuroscience, 23, 2889–2898.

    PubMed  CAS  Google Scholar 

  • Greenwood, B. N., Kennedy, S., Smith, T. P., et al. (2003b). Voluntary freewheel running selectively modulates catecholamine content in peripheral tissue and c-Fos expression in the central sympathetic circuit following exposure to uncontrollable stress in rats. Neuroscience, 120, 269–281.

    PubMed  CAS  Google Scholar 

  • Greenwood, B. N., Strong, P. V., Foley, T. E., et al. (2007a). Learned helplessness is independent of levels of brain-derived neurotrophic factor in the hippocampus. Neuroscience, 144, 1193–1208.

    PubMed  CAS  Google Scholar 

  • Greenwood, B. N., Strong, P. V., Dorey, A. A., et al. (2007b). Therapeutic effects of exercise: Wheel running reverses stress-induced interference with shuttle box escape. Behavioral Neuroscience.

  • Hajos, M., Richards, C. D., Székely, A. D., et al. (1998). An electrophysiological and neuroanatomical study of the medial prefrontal cortical projection to the midbrain raphe nuclei in the rat. Neuroscience, 87, 95–108.

    PubMed  CAS  Google Scholar 

  • Harada, T., Okagawa, S., & Kubota, K. (2004). Jogging improved performance of a behavioral branching task: Implications for prefrontal activation. Neuroscience Research, 49, 325–337.

    PubMed  Google Scholar 

  • Hervas, I., Queiroz, C. M., Adell, A., et al. (2000). Role of uptake inhibition and autoreceptor activation in the control of 5-HT release in the frontal cortex and dorsal hippocampus of the rat. British Journal of Pharmacology, 130, 160–166.

    PubMed  CAS  Google Scholar 

  • Hillman, C. H., Belopolsky, A. V., Snook, E. M., et al. (2004). Physical activity and executive control: Implications for increased cognitive health during older adulthood. Research Quarterly for Exercise and Sport, 75, 176–185.

    PubMed  Google Scholar 

  • Hillman, C. H., Castelli, D. M., & Buck, S. M. (2005). Aerobic fitness and neurocognitive function in healthy preadolescent children. Medicine and Science in Sports and Exercise, 37, 1967–1974.

    PubMed  Google Scholar 

  • Hillman, C. H., Motl, R. W., Pontifex, M. B., et al. (2006). Physical activity and cognitive function in a cross-section of younger and older community-dwelling individuals. Health Psychology, 25, 678–687.

    PubMed  Google Scholar 

  • Hillman, C. H., Snook, E. M., & Jerome, G. J. (2003). Acute cardiovascular exercise and executive control function. International Journal of Psychophysiology, 48, 307–314.

    PubMed  Google Scholar 

  • Ide, K., Horn, A., & Secher, N. H. (1999). Cerebral metabolic response to submaximal exercise. Journal of Applied Physiology, 87, 1604–1608.

    PubMed  CAS  Google Scholar 

  • Imai, H., Steindler, D. A., & Kitai, S. T. (1986). The organization of divergent axonal projections from the midbrain raphe nuclei in the rat. Journal of Comparative Neurology, 243, 363–380.

    PubMed  CAS  Google Scholar 

  • Jacobs, B. L. (1991). Serotonin and behavior: Emphasis on motor control. Journal of Clinical Psychiatry, 52, 17–23.

    PubMed  Google Scholar 

  • Jacobs, B. L., & Azmitia, E. C. (1992). Structure and function of the brain serotonin system. Physiological Reviews, 72, 165–229.

    PubMed  CAS  Google Scholar 

  • Jacobs, B. L., & Fornal, C. A. (1997). Serotonin and motor activity. Current Opinion in Neurobiology, 7, 820–825.

    PubMed  CAS  Google Scholar 

  • Jick, H., Kaye, J. A., & Jick, S. S. (2004). Antidepressants and the risk of suicidal behaviors. JAMA, 292, 338–343.

    PubMed  CAS  Google Scholar 

  • Jinks, A. L., & McGregor, I. S. (1997). Modulation of anxiety-related behaviours following lesions of the prelimbic or infralimbic cortex in the rat. Brain Research, 772, 181–190.

    PubMed  CAS  Google Scholar 

  • Kazakov, V. N., Kravtsov, P. Ya., Krakhotkina, E. D., et al. (1993). Sources of cortical, hypothalamic and spinal serotonergic projections: Topical organization within the nucleus raphe dorsalis. Neuroscience, 56, 157–164.

    PubMed  CAS  Google Scholar 

  • Kendler, K. S., Karkowski, L. M., & Prescott, C. A. (1999). Causal relationship between stressful life events and the onset of major depression. American Journal of Psychiatry, 156, 837–841.

    PubMed  CAS  Google Scholar 

  • Kennedy, S. H., Evans, K. R., Krüger, S., et al. (2001). Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression. American Journal of Psychiatry, 158, 899–905.

    PubMed  CAS  Google Scholar 

  • Kennedy, S. L., Smith, T. P., & Fleshner, M. (2005). Resting cellular and physiological effects of freewheel running. Medicine and Science in Sports and Exercise, 37, 79–83.

    PubMed  Google Scholar 

  • Kimura, F., & Nakamura, S. (1987). Postnatal development of alpha-adrenoceptor-mediated autoinhibition in the locus coeruleus. Brain Research, 432, 21–26.

    PubMed  CAS  Google Scholar 

  • Kirby, L. G., Chou-Green, J. M., Davis, K., et al. (1997). The effects of different stressors on extracellular 5-hydroxytryptamine and 5-hydroxyindoleacetic acid. Brain Research, 760, 218–230.

    PubMed  CAS  Google Scholar 

  • Kramer, A. F., Colcombe, S., Erickson, K., et al. (2002). Effects of aerobic fitness training on human cortical function: A proposal. Journal of Molecular Neuroscience, 19, 227–231.

    PubMed  CAS  Google Scholar 

  • Kramer, A. F., Colcombe, S., McAuley, E., et al. (2005). Fitness, aging and neurocognitive function. Neurobiology of Aging, 26(Suppl 1), 124–127.

    PubMed  Google Scholar 

  • Kramer, A. F., Erickson, K. I., & Colcombe, S. J. (2006). Exercise, cognition, and the aging brain. Journal of Applied Physiology, 101, 1237–1242.

    PubMed  Google Scholar 

  • Kramer, A. F., Hahn, S., Cohen, N. J., et al. (1999). Ageing, fitness and neurocognitive function. Nature, 400, 418–419.

    PubMed  CAS  Google Scholar 

  • Lawlor, D. A., & Hopker, S. W. (2001). The effectiveness of exercise as an intervention in the management of depression: Systematic review and meta-regression analysis of randomised controlled trials. BMJ, 322, 763–767.

    PubMed  CAS  Google Scholar 

  • Lee, H. S., Kim, M.-A., Valentino, R. J., et al. (2003). Glutamatergic afferent projections to the dorsal raphe nucleus of the rat. Brain Research, 963, 57–71.

    PubMed  CAS  Google Scholar 

  • Lett, B. T., Grant, V. L., Byrne, M. J., et al. (2000). Pairings of a distinctive chamber with the aftereffect of wheel running produce conditioned place preference. Appetite, 34, 87–94.

    PubMed  CAS  Google Scholar 

  • Lo, D. C. (1995). Neurotrophic factors and synaptic plasticity. Neuron, 15, 979–981.

    PubMed  CAS  Google Scholar 

  • Lowry, C. A. (2002). Functional subsets of serotonergic neurones: Implications for control of the hypothalamic–pituitary–adrenal axis. Journal of Neuroendocrinology, 14, 911–923.

    PubMed  CAS  Google Scholar 

  • Lowry, C. A., Johnson, P. L., Hay-Schmidt, A., et al. (2005). Modulation of anxiety circuits by serotonergic systems. Stress, 8, 233–246.

    Article  PubMed  CAS  Google Scholar 

  • Lucki, I. (1998). The spectrum of behaviors influenced by serotonin. Biological Psychiatry, 44, 151–162.

    PubMed  CAS  Google Scholar 

  • Maier, S. F. (1984). Learned helplessness and animal models of depression. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 8, 435–446.

    CAS  Google Scholar 

  • Maier, S. F. (1990). Role of fear in mediating shuttle escape learning deficit produced by inescapable shock. Journal of Experimental Psychology-Animal Behavior Processes, 16, 137–149.

    PubMed  CAS  Google Scholar 

  • Maier, S. F. (2001). Exposure to the stressor environment prevents the temporal dissipation of behavioral depression/learned helplessness. Biological Psychiatry, 49, 763–773.

    PubMed  CAS  Google Scholar 

  • Maier, S. F., Amat, J., Baratta, M. V., et al. (2006). Behavioral control, the medial prefrontal cortex, and resilience. Dialogues Clinical Neuroscience, 8, 397–406.

    Google Scholar 

  • Maier, S. F., Busch, C. R., Maswood, S., et al. (1995a). The dorsal raphe nucleus is a site of action mediating the behavioral effects of the benzodiazepine receptor inverse agonist DMCM. Behavioral Neuroscience, 109, 759–766.

    PubMed  CAS  Google Scholar 

  • Maier, S. F., Grahn, R. E., Kalman, B. A., et al. (1993). The role of the amygdala and dorsal raphe nucleus in mediating the behavioral consequences of inescapable shock. Behavioral Neuroscience, 107, 377–388.

    PubMed  CAS  Google Scholar 

  • Maier, S. F., Grahn, R. E., & Watkins, L. R. (1995b). 8-OH-DPAT microinjected in the region of the dorsal raphe nucleus blocks and reverses the enhancement of fear conditioning and interference with escape produced by exposure to inescapable shock. Behavioral Neuroscience, 109, 404–412.

    PubMed  CAS  Google Scholar 

  • Maier, S. F., Kalman, B. A., & Grahn, R. E. (1994). Chlordiazepoxide microinjected into the region of the dorsal reduced by inescapable shock whether administered before inescapable shock oraphe nucleus eliminates the interference with escape responding pro escape testing. Behavioral Neuroscience, 108, 121–130.

    PubMed  CAS  Google Scholar 

  • Maier, S. F., & Seligman, M. E. P. (1976). Learned helplessness: Theory and evidence. JEP: Gen., 105, 3–46.

    Google Scholar 

  • Maier, S. F., Seligman, M. E. P., & Soloman, R. L. (1969). Pavlovian fear conditioning and learned helplessness. In B. A. Campbell & R. M. Church (Eds.), Punishment. NY: Appleton-Century-Crofts.

    Google Scholar 

  • Maier, S. F., & Watkins, L. R. (1998). Stressor controllability, anxiety, and serotonin. Cognitive Therapy and Research., 22, 595–613.

    Google Scholar 

  • Maier, S. F., & Watkins, L. R. (2005). Stressor controllability and learned helplessness: The roles of the dorsal raphe nucleus, serotonin, and corticotropin-releasing factor. Neuroscience and Biobehavioral Reviews, 29, 829–841.

    PubMed  CAS  Google Scholar 

  • Malberg, J. E., & Duman, R. S. (2003). Cell proliferation in adult hippocampus is decreased by inescapable stress: Reversal by fluoxetine treatment. Neuropsychopharmacology, 28, 1562–1571.

    PubMed  CAS  Google Scholar 

  • Martinsen, E. W. (1990a) Benefits of exercise for the treatment of depression. Sports Medicine, 9, 380–389.

    PubMed  CAS  Google Scholar 

  • Martinsen, E. W. (1990b). Physical fitness, anxiety and depression. British Journal of Hospital Medicine, 43, 194, 196, 199.

    Google Scholar 

  • Martinsen, E. W. (1994). Physical activity and depression: Clinical experience. Acta Psychiatrica Scandinavica Supplement, 377, 23–27.

    CAS  Google Scholar 

  • Martinsen, E. W., Hoffart, A., & Solberg, O. (1989). Comparing aerobic with nonaerobic forms of exercise in the treatment of clinical depression: A randomized trial. Comprehensive Psychiatry, 30, 324–331.

    PubMed  CAS  Google Scholar 

  • Martinsen, E. W., & Morgan, W. P. (1997). Antidepressant effects of physical activity. In W. P. Morgan (Ed.), Physical activity and mental health. Washington, DC: Taylor & Francis.

    Google Scholar 

  • Maswood, S., Barter, J. E., Watkins, L. R., et al. (1998). Exposure to inescapable but not escapable shock increases extracellular levels of 5-HT in the dorsal raphe nucleus of the rat. Brain Research, 783, 115–120.

    PubMed  CAS  Google Scholar 

  • Maudhuit, C., Hamon, M., & Adrien, J. (1995). Electrophysiological activity of raphe dorsalis serotoninergic neurones in a possible model of endogenous depression. Neuroreport, 6, 681–684.

    PubMed  CAS  Google Scholar 

  • Moraska, A., Deak, T., Spencer, R. L., et al. (2000). Treadmill running produces both positive and negative physiological adaptations in Sprague-Dawley rats. American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 279, R1321–R1329.

    CAS  Google Scholar 

  • Morgan, W. P. (1985). Affective beneficence of vigorous physical activity. Medicine and Science in Sports and Exercise, 17, 94–100.

    PubMed  CAS  Google Scholar 

  • Mutrie, N. (2000). The relationship between physical activity and clinically defined depression. In S. J. H. Biddle, K. R. Fox, & S. H. Boutcher (Eds.), Physical activity and psychological well-being. NY: Routledge.

    Google Scholar 

  • Neeper, S. A., Gómez-Pinilla, F., Choi, J., et al. (1995). Exercise and brain neurotrophins. Nature, 373, 109.

    PubMed  CAS  Google Scholar 

  • Neeper, S. A., Gómez-Pinilla, F., Choi, J., et al. (1996). Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Research, 726, 49–56.

    PubMed  CAS  Google Scholar 

  • Ninan, P. T. (1999). The functional anatomy, neurochemistry, and pharmacology of anxiety. Journal of Clinical Psychiatry, 60(Suppl 22), 12–17.

    PubMed  CAS  Google Scholar 

  • North, T. C., McCullagh, P., & Tran, Z. V. (1990). Effect of exercise on depression. Exercise and Sport Sciences Reviews, 18, 379–415.

    PubMed  CAS  Google Scholar 

  • O’Leary, O. F., Bechtholt, A. J., Crowley, J. J., et al. (2007). Depletion of serotonin and catecholamines block the acute behavioral response to different classes of antidepressant drugs in the mouse tail suspension test. Psychopharmacology (Berl), 192, 357–371.

    CAS  Google Scholar 

  • Owens, M. J., & Nemeroff, C. B. (1994). Role of serotonin in the pathophysiology of depression: Focus on the serotonin transporter. Clinical Chemistry, 40, 288–295.

    PubMed  CAS  Google Scholar 

  • Paluska, S. A., & Schwenk, T. L. (2000). Physical activity and mental health: Current concepts. Sports Medicine, 29, 167–180.

    PubMed  CAS  Google Scholar 

  • Paxinos, G., & Watson, C. (1998). The rat brain in stereotaxic coordinates. NY: Academic Press.

    Google Scholar 

  • Petty, F., Kramer, G. L., Wu, J., et al. (1997). Posttraumatic stress and depression. A neurochemical anatomy of the learned helplessness animal model. Annals of the New York Academy of Sciences, 821, 529–532.

    PubMed  CAS  Google Scholar 

  • Peyron, C., Luppi, P. H., Fort, P., et al. (1996). Lower brainstem catecholamine afferents to the rat dorsal raphe nucleus. Journal of Comparative Neurology, 364, 402–413.

    PubMed  CAS  Google Scholar 

  • Peyron, C., Petit, J.-M. C., Jouvet, M., & Luppi, P.-H. (1998). Forebrain afferents to the rat dorsal raphe nucleus demonstrated by retrograde and anterograde tracing methods. Neuroscience, 82, 443–468.

    PubMed  CAS  Google Scholar 

  • Pollack, M. H. (2005). Comorbid anxiety and depression. Journal of Clinical Psychiatry, 66(Suppl 8), 22–29.

    PubMed  CAS  Google Scholar 

  • Quitkin, F. M., Bowden, C., Stokes, P., et al. (1996). Can the effects of antidepressants be observed in the first two weeks of treatment? Neuropsychopharmacology, 15, 390–394.

    PubMed  CAS  Google Scholar 

  • Rajkowska, G. (2000). Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biological Psychiatry, 48, 766–777.

    PubMed  CAS  Google Scholar 

  • Rajkowska, G. (2002). Cell pathology in mood disorders. Seminars in Clinical Neuropsychiatry, 7, 281–292.

    PubMed  Google Scholar 

  • Rangel, A., Villarroel, V., & Hernandez, L. (2003). Anxiolysis followed by anxiogenesis relates to coping and corticosterone after medial prefrontal cortical damage in rats. Brain Research, 992, 96–103.

    PubMed  CAS  Google Scholar 

  • Ressler, K. J., & Nemeroff, C. B. (2000). Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress and Anxiety, 12(Suppl 1), 2–19.

    Google Scholar 

  • Riad, M., Watkins, K. C., Doucet, E., et al. (2001). Agonist-induced internalization of serotonin-1a receptors in the dorsal raphe nucleus (autoreceptors) but not hippocampus (heteroreceptors). Journal of Neuroscience, 21, 8378–8386.

    PubMed  CAS  Google Scholar 

  • Riad, M., Zimmer, L., Rbah, L., et al. (2004). Acute treatment with the antidepressant fluoxetine internalizes 5-HT1A autoreceptors and reduces the in vivo binding of the PET radioligand [18F]MPPF in the nucleus raphe dorsalis of rat. Journal of Neuroscience, 24, 5420–5426.

    PubMed  CAS  Google Scholar 

  • Salmon, P. (2001). Effects of physical exercise on anxiety, depression, and sensitivity to stress: A unifying theory. Clinical Psychology Review, 21, 33–61.

    PubMed  CAS  Google Scholar 

  • Sasse, S. K., Greenwood, B. N., Masini, C. V., Nyhuis, T. J., Fleshner, M., Day, H. E. W., Campeau, S. (in press). Six weeks of voluntary wheel running facilitates hypothalamopituitary-adrenocortical axis response habituation to repeated audiogenic stress exposures in male Sprague-Dawley rats. Stress.

  • Scully, D., Kremer, J., Meade, M. M., et al. (1998). Physical exercise and psychological well being: A critical review. British Journal of Sports Medicine, 32, 111–120.

    PubMed  CAS  Google Scholar 

  • Seligman, M. E., & Beagley, G. (1975). Learned helplessness in the rat. Journal of Comparative and Physiological Psychology, 88, 534–541.

    PubMed  CAS  Google Scholar 

  • Sherman, A. D., Sacquitne, J. L., & Petty, F. (1982). Specificity of the learned helplessness model of depression. Pharmacology Biochemistry and Behavior, 16, 449–454.

    CAS  Google Scholar 

  • Shirayama, Y., Chen, A. C.-H., Nakagawa, S., et al. (2002). Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. Journal of Neuroscience, 22, 3251–3261.

    PubMed  CAS  Google Scholar 

  • Short, K. R., Patel, M. R., Lee, S. H., et al. (2000). Uncontrollable stress induced both anxiety and downregulation of dorsal raphe 5-HT1a receptors in rats: Both follow the same timecourse. Society for Neuroscience Abstracts, 26, 22–67.

    Google Scholar 

  • Simson, P. E., & Weiss, J. M. (1987). Alpha-2 receptor blockade increases responsiveness of locus coeruleus neurons to excitatory stimulation. Journal of Neuroscience, 7, 1732–1740.

    PubMed  CAS  Google Scholar 

  • Simson, P. G., Weiss, J. M., Hoffman, L. J., et al. (1986). Reversal of behavioral depression by infusion of an alpha-2 adrenergic agonist into the locus coeruleus. Neuropharmacology, 25, 385–389.

    PubMed  CAS  Google Scholar 

  • Singh, N. A., Clements, K. M., & Fiatarone, M. A. (1997). A randomized controlled trial of progressive resistance training in depressed elders. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 52, M27–M35.

    CAS  Google Scholar 

  • Smith, M. A., Makino, S., Kvetnansky, R., et al. (1995). Effects of stress on neurotrophic factor expression in the rat brain. Annals of the New York Academy of Sciences, 771, 234–239.

    PubMed  CAS  Google Scholar 

  • Soares, J., Holmes, P. V., Renner, K. J., et al. (1999). Brain noradrenergic responses to footshock after chronic activity-wheel running. Behavioral Neuroscience, 113, 558–566.

    PubMed  CAS  Google Scholar 

  • Solberg, L. C., Hortaon, T. H., & Turek, F. W. (1999). Circadian rhythms and depression: Effects of exercise in an animal model. American Journal of Physiology, 276, R152–R161.

    CAS  PubMed  Google Scholar 

  • Stamford, J. A., Davidson, C., McLaughlin, D. P., et al. (2000). Control of dorsal raphe 5-HT function by multiple 5-HT(1) autoreceptors: Parallel purposes or pointless plurality? Trends in Neurosciences, 23, 459–465.

    PubMed  CAS  Google Scholar 

  • Staub, D. R., Evans, A. K., & Lowry, C. A. (2006). Evidence supporting a role for corticotropin-releasing factor type 2 (CRF2) receptors in the regulation of subpopulations of serotonergic neurons. Brain Research, 1070, 77–89.

    PubMed  CAS  Google Scholar 

  • Suh, M. R., Jung, H. H., Kim, S. B., et al. (2002). Effects of regular exercise on anxiety, depression, and quality of life in maintenance hemodialysis patients. Renal Failure, 24, 337–345.

    PubMed  Google Scholar 

  • Suzuki, M., Miyai, I., Ono, T., et al. (2002). Running induces prefrontal activation. An optical imaging study. Abstracts Viewer/Itinerary planner, Society for neuroscience, Washington, DC, Program No. 854.10.

  • Takase, L. F., Nogueira, M. I., Bland, S. T., et al. (2005). Effect of number of tailshocks on learned helplessness and activation of serotonergic and noradrenergic neurons in the rat. Behavioural Brain Research, 162, 299–306.

    PubMed  CAS  Google Scholar 

  • Taki, Y., Kinomura, S., Awata, S., et al. (2005). Male elderly subthreshold depression patients have smaller volume of medial part of prefrontal cortex and precentral gyrus compared with age-matched normal subjects: A voxel-based morphometry. Journal of Affective Disorders, 88, 313–320.

    PubMed  Google Scholar 

  • Tavares, R. F., & Correa, F. M. (2006). Role of the medial prefrontal cortex in cardiovascular responses to acute restraint in rats. Neuroscience, 143, 231–240.

    PubMed  CAS  Google Scholar 

  • Trulson, M. E., & Crisp, T. (1984). Role of norepinephrine in regulating the activity of serotonin-containing dorsal raphe neurons. Life Sciences, 35, 511–515.

    PubMed  CAS  Google Scholar 

  • Van der Borght, K., Havekes, R., Bos, T., et al. (2007). Exercise improves memory acquisition and retrieval in the Y-maze task: Relationship with hippocampal neurogenesis. Behavioral Neuroscience, 121, 324–334.

    PubMed  Google Scholar 

  • Van Hoomissen, J. D., Holmes, P. V., Zellner, A. S., et al. (2004). Effects of beta-adrenoreceptor blockade during chronic exercise on contextual fear conditioning and mRNA for galanin and brain-derived neurotrophic factor. Behavioral Neuroscience, 118, 1378–1390.

    PubMed  Google Scholar 

  • van Praag, H. M. (2005). Can stress cause depression? World Journal of Biological Psychiatry, 6(Suppl 2), 5–22.

    PubMed  Google Scholar 

  • van Praag, H., Christie, B. R., Sejnowski, T. J. et al. (1999). Running enhances neurogenesis, learning, and long-term potentiation in mice. Proceedings of the National Academy of Sciences of the United States of America, 96, 13427–13431.

    PubMed  Google Scholar 

  • Varga, V., Székely, A. D., Csillag, A., et al. (2001). Evidence for a role of GABA interneurones in the cortical modulation of midbrain 5-hydroxytryptamine neurones. Neuroscience, 106, 783–92.

    PubMed  CAS  Google Scholar 

  • Vaynman, S., Ying, Z., & Gomez-Pinilla, F. (2004). Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. European Journal of Neuroscience, 20, 2580–2590.

    PubMed  Google Scholar 

  • Vertes, R. P. (2004). Differential projections of the infralimbic and prelimbic cortex in the rat. Synapse, 51, 32–58.

    PubMed  CAS  Google Scholar 

  • Walker, D. L., Toufexis, D. J., & Davis, M. (2003). Role of the bed nucleus of the stria terminalis versus the amygdala in fear, stress, and anxiety. European Journal of Pharmacology, 463, 199–216.

    PubMed  CAS  Google Scholar 

  • Weiss, J. M., Bonsall, R. W., Demetrikopoulos, M. K., et al. (1998). Galanin: A significant role in depression? Annals of the New York Academy of Sciences, 863, 364–382.

    PubMed  CAS  Google Scholar 

  • Weiss, J. M., Boss-Williams, K., Moore, J., et al. (2005). Testing the hypothesis that locus coeruleus hyperactivity produces depression-related changes via galanin. Neuropeptides, 39, 281–287.

    PubMed  CAS  Google Scholar 

  • Weiss, J. M., Demetrikoppoulos, M. K., West, C. H. K., et al. (1996). Hypothesis linking the noradrenergic and dopaminergic systems in depression. Depression, 3, 225–245.

    Google Scholar 

  • Weiss, J. M., Goodman, P. A., Losito, B. G., et al. (1981). Behavioral depression produced by an uncontrollable stressor: Relationship to norepinephrine, dopamine, and serotonin levels in various regions of the rat brain. Brain Research Reviews, 3, 167–205.

    CAS  Google Scholar 

  • Weiss, J. M., & Kilts, C. D. (1998). Animal models of depression and schizophrenia. In C. B. Nemeroff & A. F. Schatzberg (Eds.), The American psychiatric press textbook of psychopharmacology (2nd ed., pp. 89–131). Washington, DC: American Psychiatric Press Inc.

    Google Scholar 

  • Weiss, J. M., & Simson, P. G. (1985). Neurochemical basis of stress-induced depression. Psychopharmacology Bulletin, 21, 447–457.

    PubMed  CAS  Google Scholar 

  • Weiss, J. M., & Simson, P. G. (1986). Depression in an animal model: Focus on the locus ceruleus. Ciba Foundation Symposia, 123, 191–215.

    CAS  PubMed  Google Scholar 

  • Werme, M., Messer, C., Olso, L., et al. (2002). Delta FosB Regulates Wheel Running. Journal of Neuroscience, 22, 8133–8138.

    PubMed  CAS  Google Scholar 

  • Williams, J. L., & Maier, S. F. (1977). Transituational immunization and therapy of learned helplessness in the rat. Journal of Experimental Psychology-Animal Behavior Processes, 3, 240–253.

    Google Scholar 

  • Willner, P. (1986). Validation criteria for animal models of human mental disorders: Learned helplessness as a paradigm case. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 10, 677–690.

    CAS  Google Scholar 

  • Zheng, H., Liu, Y., Li, W., et al. (2006). Beneficial effects of exercise and its molecular mechanisms on depression in rats. Behavioural Brain Research, 168, 47–55.

    PubMed  CAS  Google Scholar 

  • Zhu, M. Y., Klimek, V., Dilley, G. E., et al. (1999). Elevated levels of tyrosine hydroxylase in the locus coeruleus in major depression. Biological Psychiatry, 46, 1275–1286.

    PubMed  CAS  Google Scholar 

  • Zienowicz, M., Wislowska-Stanek, A., Lehner, M., et al. (2006). Fluoxetine-induced anxiety and nervousness. Pharmacology Report, 58, 115–119.

    CAS  Google Scholar 

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Greenwood, B.N., Fleshner, M. Exercise, Learned Helplessness, and the Stress-Resistant Brain. Neuromol Med 10, 81–98 (2008). https://doi.org/10.1007/s12017-008-8029-y

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