Differential involvement of the endocannabinoid system in short- and long-term expression of incentive learning supported by nicotine in rats.
BACKGROUND
We previously reported that the CB1 cannabinoid receptor antagonist, rimonabant, impaired the acquisition and the short-term (24 h), but not long-term (3 weeks), expression of conditioned place preference (CPP) induced by nicotine in rats.


OBJECTIVE
To assess the time interval of efficacy of a single pretest injection of rimonabant to abolish nicotine-CPP, and the effects of chronic CB1 receptor blockade on long-term expression of nicotine-CPP.


METHODS
Wistar rats were conditioned to nicotine (0.06 mg/kg, subcutaneous) using an unbiased one-compartment procedure. Two test sessions were conducted 24 h (without injection) and 1, 2, or 3 weeks later. Rimonabant (3 mg/kg, intraperitoneal) or vehicle was administered daily between the two test sessions. In addition, the CB1-stimulated [(35)S]GTP-gamma-S binding was assessed in rats from the 3-week experiment.


RESULTS
The capacity of a single injection of rimonabant (3 mg/kg, 30 min pretest) to block the expression of nicotine-CPP disappeared within 1 week after conditioning. Daily administrations of rimonabant for 6, 13, or 20 days post-acquisition did not impair nicotine-CPP but allowed an additional pretest injection of rimonabant to retain its capacity to abolish long-term expression of nicotine-CPP. The CB1 receptor-mediated G-protein signaling was not altered in various brain areas of rats given rimonabant for 3 weeks.


CONCLUSIONS
The endocannabinoid system is essential to the expression of nicotine-CPP during less than 1 week after conditioning but not later. However, endocannabinoid-dependent mechanisms are critically involved in the development of the neuroadaptive changes responsible for the shift from CB1-dependent to CB1-independent expression of nicotine incentive learning.
Forget
Benoît
B
INSERM, U677, Paris, F-75013, France.
Barthélémy
Sandrine
S
Saurini
Françoise
F
Hamon
Michel
M
Thiébot
Marie-Hélène
MH
D000818:Animals; D001245:Association Learning / Q000187:drug effects*; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects*; D048588:Benzoxazines; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D003214:Conditioning, Classical / Q000187:drug effects; D063388:Endocannabinoids; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D008297:Male; D009025:Morpholines / Q000378:metabolism; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077285:Rimonabant; D013997:Time Factors
D048588:Benzoxazines; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D009025:Morpholines; D009281:Naphthalenes; D018722:Nicotinic Agonists; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D009538:Nicotine; D000077285:Rimonabant