Modification of behavioral effects of 8-hydroxy-2-(di-n-propylamino)tetralin following chronic ethanol consumption in the rat: evidence for the involvement of 5-HT_1A receptors in ethanol dependence

Behavioral effects induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; i.e., lower lip retraction, flat body posture, and forepaw treading) were examined in rats during ethanol withdrawal following a 2-week period of access to a liquid diet containing 9% (v/v) ethanol. After an 18 h withdrawal period, tolerance to 8-OH-DPAT-induced flat body posture and, conversely, sensitization to the effects of 8-OH-DPAT on lower lip retraction were observed in the 9% ethanol group as compared to control rats fed an isocaloric diet. In contrast, 8-OH-DPAT-induced forepaw treading in the 9% ethanol group was not significantly different in comparison to control rats. Plasma corticosterone levels were significantly higher in the ethanol-exposed group than in control animals, an effect which was not additive with the increase in corticosterone levels normally observed after the administration of low doses of 8-OH-DPAT. Altered flat body posture and lower lip retraction responses to a submaximal dose of 8-OH-DPAT (2.5 mg/kg i.p.) were still observed as late as 3 days after withdrawal of the 9% ethanol liquid diet, but were no longer apparent at 7 days. Interestingly, prominent ethanol withdrawal signs such as tremor and rigidity, while occurring on the first day, were completely absent on the third day. Taken together, these results indicate that chronic ethanol exposure differentially alters sensitivity to several pharmacological effects of the 5-HT_1A receptor ligand 8-OH-DPAT. They further support the involvement of 5-HT (5-hydroxytryptamine, serotonin) systems in alcohol abuse and therapeutic interventions using 5-HT_1A ligands.