Gamma-hydroxybutyric acid intake in ethanol-preferring sP and -nonpreferring sNP rats

Gamma-hydroxybutyric acid (GHB) and ethanol share several pharmacological similarities, suggesting that GHB may exert ethanol-like effects in the central nervous system. The present study was designed to test whether selectively bred ethanol-preferring rats would, unlike ethanol-nonpreferring ones, self-administer GHB, consistent with their higher preference for ethanol. Male ethanol-naive Sardinian alcohol-preferring (sP) and Sardinian alcohol-nonpreferring (sNP) rats were used. In Experiment 1, GHB solution (1% (w/v) in water) was initially offered as the sole fluid available for 14 consecutive days and then presented under the two-bottle, free-choice regimen, one bottle containing water and the other the GHB solution, for an additional 14 consecutive days. During the free-choice phase, high preference for GHB and intake of pharmacologically relevant daily doses of GHB developed in both rat lines, presumably because the 14-day no-choice period would unmask the reinforcing properties of GHB and lead to acquisition of GHB preference also in the supposedly less susceptible sNP rats. In Experiment 2, the forced GHB drinking phase was reduced to 3 days. Under the subsequent free-choice regimen, daily GHB preference and intake were initially low in both sP and sNP rats; however, after approximately 10 days, GHB preference and intake in sP rats rose progressively and then stabilized to significantly higher levels than in sNP rats throughout the entire free-choice phase. It is likely that episodic binges of GHB intake occurring during the first 10 days resulted in experiencing the reinforcing properties of GHB by sP but not sNP rats. The results of the present study suggest that a) sP rats are genetically more sensitive to the reinforcing effects of both ethanol and GHB than sNP rats; and b) disclosure of the higher sensitivity of sP rats to the reinforcing effects of GHB is a function of the length of the induction procedure. The results are also discussed in terms of differences in GHB receptors contributing to the predisposition to ethanol preference and avoidance, respectively.