Marijuana's interaction with brain reward systems: Update 1991

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Abstract

The most pervasive commonality amongst noncannabinoid drugs of abuse is that they enhance electrical brain stimulation reward and act as direct or indirect dopamine agonists in the reward relevant dopaminergic projections of the medial forebrain bundle (MFB). These dopaminergic projections constitute a crucial drug sensitive link in the brain's reward circuitry, and abused drugs derive significant abuse liability from enhancing these circuits. Marijuana and other cannabinoids were long considered “anomalous” drugs of abuse, lacking pharmacological interaction with these brain reward substrates. It is now clear, however, that Δ9-tetrahydrocannab (Δ9-THC), marijuana's principal psychoactive constituent, acts on these brain reward substrates in strikingly similar fashion to noncannabinoid drugs of abuse. Specifically, Δ9-THC enhances MFB electrical brain stimulation reward, and enhances both basal and stimulated dopamine release in reward relevant MFB projection loci. Furthermore, Δ9-THC's actions on these mechanisms is naloxone blockable, and Δ9-THC modulates brain μ and δ opioid receptors. This paper reviews these data, suggests that marijuana's interaction with brain reward systems is fundamentally similar to that of other abused drugs, and proposes a specific neural model of that interaction.

References (116)

  • I.D. Hirschhorn et al.

    Evidence for a role of endogenous opioids in the nigrostriatal system: Influence of naloxone and morphine on nigrostriatal dopaminergic supersensitivity

    Brain Res.

    (1983)
  • D.W. Hommer et al.

    The action of opiates in the rat substantia nigra: An electrophysiological analysis

    Peptides

    (1983)
  • P. Hunt et al.

    Dopamine reuptake inhibitors and releasing agents differentiated by the use of synaptosomes and field-stimulated brain slices in vitro

    Biochem. Pharmacol.

    (1979)
  • A. Imperato et al.

    Nicotine preferentially stimulates dopamine release in the limbic system of freely moving rats

    Eur. J. Pharmacol.

    (1986)
  • H. Khachaturian et al.

    Anatomy of the CNS opioid systems

    Trends Neurosci.

    (1985)
  • S.A. Lorens et al.

    Naloxone blocks the excitatory effect of ethanol and chlordiazepoxide on lateral hypothalamic self-stimulation behavior

    Life Sci.

    (1978)
  • A. Mansour et al.

    Anatomy of CNS opioid receptors

    Trends Neurosci.

    (1988)
  • G.J. Mogenson et al.

    Self-stimulation of the nucleus accumbens and ventral tegmental area of Tsai attenuated by microinjections of spiroperidol into the nucleus accumbens

    Brain Res.

    (1979)
  • C. Moret et al.

    Sensitivity of the response of 5-HT autoreceptors to drugs modifying synaptic availability of 5-HT

    Neuropharmacology

    (1988)
  • J.M. Nazzaro et al.

    GABA antagonism lowers self-stimulation thresholds in the ventral tegmental area

    Brain Res.

    (1980)
  • A.G. Phillips et al.

    Reinforcing effects of morphine microinjection into the ventral tegmental area

    Pharmacol. Biochem. Behav.

    (1980)
  • H. Pollard et al.

    Localization of opiate receptors and enkephalins in the rat striatum in relationship with the nigrostriatal dopaminergic system: Lesion studies

    Brain Res.

    (1978)
  • M.C. Ritz et al.

    Genetic differences in the establishment of ethanol as a reinforcer

    Pharmacol. Biochem. Behav.

    (1986)
  • H. Rosenkrantz et al.

    Oral Δ9-tetrahydrocannabinol toxicity in rats treated for periods up to six months

    Toxicol. Appl. Pharmacol.

    (1975)
  • T.F. Seeger et al.

    Enhancement of self-stimulation behavior in rats and monkeys after chronic neuroleptic treatment: Evidence for mesolimbic supersensitivity

    Brain Res.

    (1979)
  • T.F. Seeger et al.

    Selective inhibition of mesolimbic behavioral supersensitivity by naloxone

    Eur. J. Pharmacol.

    (1980)
  • F.C. Tulunay et al.

    Antagonism by chlornaltrexamine of some effects of Δ9-tetrahydrocannabinol in rats

    Eur. J. Pharmacol.

    (1981)
  • B.H.C. Westerink et al.

    Dopamine re-uptake inhibitors show inconsistent effects on the in vivo release of dopamine as measured by intracerebral dialysis in the rat

    Eur. J. Pharmacol.

    (1987)
  • N.M. Bhargava

    Inhibition of naloxone-induced withdrawal in morphine dependent mice by 1-trans-Δ9-tetrahydrocannabinol

    Eur. J. Pharmacol.

    (1976)
  • M. Bidaut-Russell et al.

    Cannabinoid receptors and modulation of cyclic AMP accumulation in the rat brain

    J. Neurochem.

    (1990)
  • J. Chen et al.

    In vivo brain microdialysis study of phencyclidine on presynaptic dopamine efflux in rat caudate nucleus

    Soc. Neurosci. Abstr.

    (1988)
  • J. Chen et al.

    In vivo brain microdialysis studies of Δ9-tetrahydrocannabinol on presynaptic dopamine efflux in nucleus accumbens of the Lewis rat

    Soc. Neurosci. Abstr.

    (1989)
  • J. Chen et al.

    Δ9-tetrahydrocannabinol produces naloxone-blockable enhancement of presynaptic dopamine efflux in nucleus accumbens of conscious, freely-moving rats as measured by intracerebral microdialysis

    Psychopharmacology (Berlin)

    (1990)
  • T. Chow et al.

    Solubilization and preliminary characterization of mu and kappa opiate receptor subtypes from rat brain

    Mol. Pharmacol.

    (1983)
  • L.X. Cubeddu et al.

    Frequency-dependent effects of neuronal uptake inhibitors on the autoreceptor-mediated modulation of dopamine and acetylcholine release from the rabbit striatum

    J. Pharmacol. Exp. Ther.

    (1983)
  • A.C. Cuello et al.

    Evidence for a long leu-enkephalin striopallidal pathway in rat brain

    Nature

    (1978)
  • W.A. Devane et al.

    Determination and characterization of a cannabinoid receptor in rat brain

    Mol. Pharmacol.

    (1988)
  • G. Di Chiara et al.

    Preferential stimulation of dopamine release in the nucleus accumbens by opiates, alcohol, and barbiturates: Studies with transcerebral dialysis in freely moving rats

    Ann. NY Acad. Sci.

    (1986)
  • R.U. Esposito et al.

    Effects of d-amphetamine and naloxone on brain stimulation reward

    Psychopharmacology (Berlin)

    (1980)
  • H.C. Fibiger et al.

    Mesotelencephalic dopamine systems and reward

    Ann. NY Acad. Sci.

    (1988)
  • P.J. Fray et al.

    Nigral transplants reinnervating the dopamine-depleted neostriatum can sustain intracranial self-stimulation

    Science

    (1983)
  • C.R. Gallistel

    Self-stimulation in the rat: Quantitative characteristics of the reward pathway

    J. Comp. Physiol. Psychol.

    (1978)
  • C.R. Gallistel et al.

    A portrait of the substrate for self-stimulation

    Psychol. Rev.

    (1981)
  • A.M. Galzin et al.

    Presynaptic inhibition of dopamine receptor agonists of noradrenergic neurotransmission in the rabbit hypothalamus

    J. Pharmacol. Exp. Ther.

    (1982)
  • A.M. Galzin et al.

    Interaction between tricyclic and nontricyclic 5-hydroxytryptamine uptake inhibitor and the presynaptic 5-hydroxytryptamine inhibitory autoreceptors in the rat hypothalamus

    J. Pharmacol. Exp. Ther.

    (1985)
  • E.L. Gardner et al.

    Facilitation of brain stimulation reward by Δ9-tetrahydrocannabinol

    Psychopharmacology (Berlin)

    (1988)
  • E.L. Gardner et al.

    Strain-specific facilitation of brain stimulation reward by Δ-9-tetrahydrocannabinol in laboratory rats

  • E.L. Gardner et al.

    Strain-specific sensitization of brain stimulation reward by Δ9-tetrahydrocannabinol in laboratory rats

    Psychopharmacology (Berlin)

    (1988)
  • E.L. Gardner et al.

    Strain-specific facilitation of brain stimulation reward by Δ9-tetrahydrocannabinol in laboratory rats is mirrored by strain-specific facilitation of presynaptic dopamine efflux in nucleus accumbens

    Soc. Neurosci. Abstr.

    (1989)
  • E.L. Gardner et al.

    Facilitation of brain stimulation reward by Δ9-tetrahydrocannabinol is mediated by an endogenous opioid mechanism

    Adv. Biosci.

    (1989)
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