title: Cannabinoids inhibit excitatory inputs to neurons in the shell of the nucleus accumbens: an in vivo electrophysiological study.
abstract: The nucleus accumbens (NAc) represents a critical site for the rewarding properties of diverse classes of drugs of abuse. Glutamatergic afferents to the NAc are involved in the actions of psychostimulants and opioids, while the potentiation of dopaminergic neurotransmission in the NAc is a common feature of abused drugs, including cannabinoids. Cannabinoid receptors (CB1) are densely expressed in regions that provide excitatory innervation to the NAc, such as the amygdala, the cortex and the hippocampus. Recent in vitro evidence suggests that indeed cannabinoids modulate glutamatergic synapses in the NAc. In this study we recorded extracellularly from neurons in the shell of the NAc which responded to the stimulation of the baso-lateral amygdala (BLA) or the medial prefrontal cortex (PFC) in urethane anaesthetized rats. BLA or PFC stimulation induced generation of action potentials in NAc neurons. This excitatory effect was strongly inhibited by the synthetic cannabinoid agonists WIN 55212,2 (0.062-0.25 mg/kg, i.v.) and HU-210 (0.125-0.25 mg/kg, i.v.) or the psychoactive principle of Cannabis delta(9)-tetrahydrocannabinol (1.0 mg/kg, i.v.). Neither the D1 or D2 dopamine receptor antagonists (SCH23390 0.5-1.0 mg/kg, sulpiride 5-10 mg/kg, i.v.) or the opioid antagonist naloxone (1.0 mg/kg, i.v.) were able to reverse the action of cannabinoids, while the selective CB1 receptor antagonist/reverse agonist SR141716A (0.5 mg/kg, i.v.) fully suppressed the action of cannabinoid agonists, whereas per se had no significant effect. These results provide evidence that cannabinoids, in common with other drugs of abuse, in vivo strongly inhibit the excitability of neurons in the shell of the NAc.
authors.affiliation: B.B. Brodie Department of Neuroscience, University of Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy. mpistis@unica.it
authors.forename: Marco
authors.initials: M
authors.lastname: Pistis
authors.forename: Anna Lisa
authors.initials: AL
authors.lastname: Muntoni
authors.forename: Giuliano
authors.initials: G
authors.lastname: Pillolla
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Gessa
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000679:Amygdala / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D048588:Benzoxazines; D002186:Cannabinoids / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism; D000077285:Rimonabant; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D000700:Analgesics; D048588:Benzoxazines; D002186:Cannabinoids; D018492:Dopamine Antagonists; D009025:Morpholines; D009281:Naphthalenes; D009292:Narcotic Antagonists; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D018698:Glutamic Acid; 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; C062018:HU 211; D000077285:Rimonabant; D004298:Dopamine