Kelaï Sabah, Hanoun Naïma, Aufrère Gilles, Beaugé Françoise, Hamon Michel, Lanfumey Laurence
UMR 677 INSERM-UPMC, Faculté de Médecine Pierre et Marie Curie, Site Pitié-Salpêtrière, IFR 70 des Neurosciences, Paris, France.
J Neurochem. 2006 Oct;99(1):308-20. doi: 10.1111/j.1471-4159.2006.04054.x.
Because cannabinoid and serotonin (5-HT) systems have been proposed to play an important role in drug craving, we investigated whether cannabinoid 1 (CB1) and 5-HT(1A) receptor ligands could affect voluntary alcohol intake in two mouse strains, C57BL/6 J and DBA/2 J, with marked differences in native alcohol preference. When offered progressively (3-10% ethanol) in drinking water, in a free-choice procedure, alcohol intake was markedly lower (approximately 70%) in DBA/2 J than in C57BL/6 J mice. In DBA/2 J mice, chronic treatment with the cannabinoid receptor agonist WIN 55,212-2 increased alcohol intake. WIN 55,212-2 effect was prevented by concomitant, chronic CB1 receptor blockade by rimonabant or chronic 5-HT(1A) receptor stimulation by 8-hydroxy-2-(di-n-propylamino)-tetralin, which, on their own, did not affect alcohol intake. In C57BL/6 J mice, chronic treatment with WIN 55,212-2 had no effect but chronic CB1 receptor blockade or chronic 5-HT(1A) receptor stimulation significantly decreased alcohol intake. Parallel autoradiographic investigations showed that chronic treatment with WIN 55,212-2 significantly decreased 5-HT(1A)-mediated [35S]guanosine triphosphate-gamma-S binding in the hippocampus of both mouse strains. Conversely, chronic rimonabant increased this binding in C57BL/6 J mice. These results show that cannabinoid neurotransmission can exert a permissive control on alcohol intake, possibly through CB1-5-HT(1A) interactions. However, the differences between C57BL/6 J and DBA/2 J mice indicate that such modulations of alcohol intake are under genetic control.
由于大麻素和5-羟色胺（5-HT）系统被认为在药物成瘾中起重要作用，我们研究了大麻素1（CB1）和5-HT（1A）受体配体是否会影响两种小鼠品系（C57BL/6 J和DBA/2 J）的自愿酒精摄入量，这两种品系在天然酒精偏好上有显著差异。在自由选择程序中，当饮用水中逐渐添加（3%-10%乙醇）时，DBA/2 J小鼠的酒精摄入量明显低于C57BL/6 J小鼠（约70%）。在DBA/2 J小鼠中，大麻素受体激动剂WIN 55,212-2的慢性治疗增加了酒精摄入量。利莫那班的慢性CB1受体阻断或8-羟基-2-（二正丙基氨基）-四氢萘的慢性5-HT（1A）受体刺激可预防WIN 55,212-2的作用，而单独使用这两种药物时，均不影响酒精摄入量。在C57BL/6 J小鼠中，WIN 55,212-2的慢性治疗没有效果，但慢性CB1受体阻断或慢性5-HT（1A）受体刺激显著降低了酒精摄入量。平行放射自显影研究表明，WIN 55,212-2的慢性治疗显著降低了两种小鼠品系海马中5-HT（1A）介导的[35S]鸟苷三磷酸-γ-S结合。相反，慢性利莫那班增加了C57BL/6 J小鼠中的这种结合。这些结果表明，大麻素神经传递可能通过CB1-5-HT（1A）相互作用对酒精摄入量施加许可性控制。然而，C57BL/6 J和DBA/2 J小鼠之间的差异表明，这种酒精摄入量的调节受基因控制。
