Cannabinoid-serotonin interactions in alcohol-preferring vs. alcohol-avoiding mice.
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.
Kelaï
Sabah
S
UMR 677 INSERM-UPMC, Faculté de Médecine Pierre et Marie Curie, Site Pitié-Salpêtrière, IFR 70 des Neurosciences, Paris, France.
Hanoun
Naïma
N
Aufrère
Gilles
G
Beaugé
Françoise
F
Hamon
Michel
M
Lanfumey
Laurence
L
D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000428:Alcohol Drinking / Q000378:metabolism*; D000437:Alcoholism / Q000378:metabolism*; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D002186:Cannabinoids / Q000378:metabolism*; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D013695:Temperance
D002186:Cannabinoids; D043884:Receptor, Cannabinoid, CB1; D011985:Receptors, Serotonin; D012701:Serotonin; D000426:Alcohol Dehydrogenase; D000445:Aldehyde Oxidoreductases; C018699:aldehyde dehydrogenase (NAD(P)+)