High sensitivity to γ-hydroxybutyric acid in ethanol-preferring sP rats

Sensitivity to the sedative effect of gamma-hydroxybutyric acid (GHB), an endogenous constituent of mammalian brain as well as an effective drug in the pharmacotherapy of alcoholism, was evaluated in rats of the selectively bred, ethanol-preferring sP and non-preferring sNP lines. GHB (0.75 and 1.0 g/kg) was administered i.p. to ethanol-naive sP and sNP rats. Times to lose (onset) and recover (sleep time) the righting reflex following GHB injection were measured. At both doses, sP rats showed a greater sensitivity to the effects of GHB than did sNP rats, as evidenced by significantly shorter onset and longer sleep time. The results of the present study indicate that genetically controlled sensitivity to the sedative effect of GHB is positively correlated to ethanol preference in sP and sNP rats and suggest a possible involvement of the brain GHB system in predisposition to ethanol preference.