QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.106.116830v1 321/3/1127    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Solinas, M. Articles by Goldberg, S. R. Search for Related Content PubMed PubMed Citation Articles by Solinas, M. Articles by Goldberg, S. R.

BEHAVIORAL PHARMACOLOGY

Nicotinic Facilitation of 9-Tetrahydrocannabinol Discrimination Involves Endogenous Anandamide

Laboratoire de Biologie et Physiologie Cellulaires, Centre National de la Recherche Scientifique-VMR6187, Université de Poitiers, Poitiers, France (M.So.); Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch (M.So., M.Sc., C.E.W., S.R.G.) and Psychobiology Section, Medications Discovery Research Branch (G.T.), Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland; and B.B. Brodie Department of Neuroscience, University of Cagliari, Cagliari, Italy (M.Sc., W.F.)

Systemic administration of the main active ingredient in cannabis, 9-tetrahydrocannabinol (THC), alters extracellular levels of acetylcholine in several brain areas, suggesting an involvement of the cholinergic system in the psychotropic effects of cannabis. Here, we investigated whether drugs acting at either nicotinic or muscarinic receptors can modulate the discriminative effects of THC. In rats that had learned to discriminate effects of 3 mg/kg i.p. injections of THC from injections of vehicle, the nicotinic agonist nicotine (0.1-0.56 mg/kg subcutaneous) and the muscarinic agonist pilocarpine (0.3-3 mg/kg i.p.) did not produce THC-like effects, but they both potentiated the discriminative effects of low doses of THC (0.3-1 mg/kg). Neither the nicotinic antagonist mecamylamine (1-5.6 mg/kg i.p.) nor the muscarinic antagonist scopolamine (0.01-0.1 mg/kg i.p.) altered the discriminative effects of THC, but they blocked the potentiation of discriminative effects of THC by nicotine and pilocarpine, respectively. The cannabinoid CB₁ antagonist rimonabant (1 mg/kg i.p.) reversed nicotine- but not pilocarpine-induced potentiation of THC discrimination, suggesting that nicotine potentiation is, at least in part, mediated by release of endogenous cannabinoids in the brain. In addition, when metabolic degradation of the endogenous cannabinoid anandamide was blocked by the fatty acid amide hydrolase inhibitor cyclohexyl carbamic acid 3'-carbamoylbiphenil-3-yl-ester (URB-597; 0.3 mg/kg i.p.) nicotine, but not pilocarpine, produced significant THC-like discriminative effects that were antagonized by rimonabant. Our results suggest that nicotinic and muscarinic cholinergic receptors modulate the discriminative effects of THC by fundamentally different mechanisms. Nicotinic, but not muscarinic, modulation of THC discrimination involves elevations in endogenous levels of anandamide.

Address correspondence to: Dr. Marcello Solinas, Laboratoire de Biologie et Physiologie Cellulaires, Centre National de la Recherche Scientifique-6187, University of Poitiers, 40 Avenue du Recteur Pineau, 86022, Poitiers, France. E-mail: marcello.solinas{at}univ-poitiers.fr