Increase in meso-prefrontal dopaminergic activity after stimulation of CB1 receptors by cannabinoids.
The intravenous administration of the psychoactive constituent of marijuana, delta9-tetrahydrocannabinol (delta9-THC) (62.5-1000 microg/kg), and the synthetic cannabinoid agonist WIN 55212,2 (WIN) (62.5-500 microg/kg), produced a dose-related increase in the firing rate and burst firing in the majority of antidromically identified meso-prefrontal dopaminergic neurons. In a restricted number of neurons (n=4), WIN administration did not increase firing rate but produced an increment of bursting activity. These effects of the cannabinoids were reversed by the intravenous administration of SR 141716 A, a selective cannabinoid antagonist (1 mg/kg), per se ineffective to modify the electrical activity of dopaminergic neurons. The results indicate that stimulation of cannabinoid CB1 receptors produces an activation of meso-prefrontal dopaminergic transmission. Considering that supranormal stimulation of D1 dopamine receptors in the prefrontal cortex has been shown to impair working memory, the present results suggest that the negative effects of cannabinoids on cognitive processes might be related to the activation of dopaminergic transmission in the prefrontal cortex.
Diana
M
M
Department of Drug Sciences, University of Sassari, Italy. dsfdiana@ssmain.uniss.it
Melis
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M
Gessa
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GL
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D048588:Benzoxazines; D002186:Cannabinoids / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D007275:Injections, Intravenous; D008297:Male; D008839:Microelectrodes; D009025:Morpholines / Q000008:administration & dosage / Q000494:pharmacology; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists* / Q000378:metabolism*; D000077285:Rimonabant
D048588:Benzoxazines; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000077285:Rimonabant; D004298:Dopamine