Cannabinoids excite dopamine neurons in the ventral tegmentum and substantia nigra.
Extracellular recordings were used to determine the effects of cannabinoids on the activity of dopamine neurons within the ventral tegmental area (VTA) and substantia nigra pars compacta (SNC). Systemic administration of the natural psychoactive cannabinoid delta 9-tetrahydrocannabinol (delta 9-THC) and the synthetic cannabimimetic aminoalkylindole WIN 55,212-2 produced dose-dependent increases in firing rate and burst firing in both neuronal populations. These effects appear to be specific as the non-psychoactive cannabidiol and the inactive enantiomer WIN 55,212-3 failed to alter either parameter of neuronal excitability. Furthermore, dopamine neurons in the VTA were more sensitive than those in the SNC to the stimulatory actions of delta 9-THC. These results may provide a mechanism by which psychoactive cannabinoids increase extracellular dopamine levels in mesolimbic and striatal tissues, and thereby contribute to the reinforcing effects of marijuana.
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Department of Pharmacology, College of Medicine, University of Arizona, Tucson 85724, USA.
Dillon
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Wu
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D000700:Analgesics / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D048588:Benzoxazines; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000502:physiology*
D000700:Analgesics; D048588:Benzoxazines; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D013759:Dronabinol; D004298:Dopamine