Fluoxetine treatment reduces alcohol consumption in females, but not in males, rats exhibiting reserpine-induced depression

CALLIARI A; PAUTASSI R.M.; RUIZ P

Berlin

Congreso; World Congress on Behavior and Cognitive Therapies WCBCT2019; 2019

IntroductionMood disorders exhibit comorbidity with alcohol use disorders (AUD), especially in adolescence. The reasons underlying the associationbetween mood disorders, notably depression, and AUD are not well understood, although a long-standing theory (the self-medicationhypothesis) suggests that alcohol intake in depressed individuals is driven by the pharmacological effects of the drug, as a mean to restorenormal mood functioning.MethodWe analyzed this hypothesis in a pre-clinical model of adolescence. Specifically, we pharmacologically induced depression in adolescentrats, males and females, by administering reserpine (RES 0.0 or 1.0 mg/kg/day, i.p.) on postnatal days (PDs) 30 to 33; and aimed atinhibiting the effects of RES by treatment with fluoxetine (FLUOX, 0.0 or 10.0 mg/kg/day, i.p.), on PDs 34-37. Experimental depression wasconfirmed via a behavioral screening and the rats were subsequently tested for ethanol (alcohol) intake in two-bottle choice (5% ethanol vs.water) tests.ResultsEthanol intake on a gram per kilogram basis was greater in female, but not in male, rats treated with RES than in their correspondingcontrols. This sex-dependent effect was inhibited by FLUOX. An ANOVA yielded a significant effect of Sex and a significant REStreatment x FLUOX treatment x Sex interaction. Males drank significantly lower quantities of ethanol than did females. More important, theFisher post-hoc tests indicated that females given RES followed by vehicle on PDs 34-37 drank more than females also treated with RES butthen administered FLUOX on PDs 34-37. The ANOVA for ethanol percent preference yielded significant main effects of Sex, Reserpine andSession.DiscussionThese results are consistent with several pre-clinical studies showing that, in a variety of test situations and unlike the pattern found inhumans, female rats drank more in gram per kilogram basis than male counterparts. The results also show that experimental depressionenhanced ethanol intake in the females and that the selective serotonin reuptake inhibitor fluoxetine was useful to block this effect. Thisfinding is clinically relevant for the designs of new pharmacological therapies for AUD