Sex-related alcohol consumption induced by restraint stress in adolescent rats

WILLE-BILLE, ARANZA; PAUTASSI R.M.

Cordoba

Workshop; Workshop: The neurohumoral control of body fluid and cardiovascular homeostasis in males and females - vive la difference!; 2019

INIMEC-CONICET-UNC

Adolescence is a developmental stage associated with remodeling of brain architecture,and involves behavioral and hormonal changes (Spear, 2000). These changes may underliethe greater vulnerability to drug abuse observed during this stage (Spear, 2000; Andersen,2003; Dahl, 2004). Preclinical and animal studies suggest that adolescents are uniquelysensitive to ethanol´s pharmacological effects (anxiolytic effects) (Acevedo, 2014) and thatthis pattern of response may put them at risk for alcohol initiation and escalation (Spear,2014). Adolescent rats exhibit, compared to adults, greater sensitivity to the appetitive(Pautassi, 2008) and social facilitating effects of ethanol (Varlinskaya, 2002); but less sensitiveto the aversive motivational effects of the drug (Anderson, 2010). Stress is one of the riskfactors that promotes greater engagement and escalation into alcohol consumption (Sinha,2003; Polter, 2014), and evidence suggests that adolescents could be more sensitive to stressthan adults (Stone, 1997). Stress can enhance the appetitive reinforcing and decrease theaversive effects of ethanol (Bertoglio, 2002). We analyzed the permissive effects of stress onalcohol intake, in adolescents; and scrutinize possible sex-differences in this effect. In Experiment 1, male and female rats, 30 days-old, were subjected to five daily sessionsof 120 minutes of restraint stress, using PVC tubes 20 cm long and 5-8 cm wide (Fig. 1); vs.control. The alcohol intake began 72 hours after the last stress session, and lasted 2 weeks,with intermittent, 18 hours per day, three times a week. Solutions were ethanol 4% v/v onthe first week, and 5% v/v in the second; vs. vehicle (water). Experiment 2 replicated thisprocedure on female rats administrated with 10 mg/kg kappa antagonist, norBinaltorphimine (nor-BNI), 24 hours before the first stress session; vs. vehicle (salinesolution). Body weight was registered before each stress session, as well g/kg alcoholconsumed and percent preference, and body weight was analyzed as a percentageincrease from day 1 of stress to day 5 [(day5weight ? day1weight)/day1*100].Experiment 1 showed a significative interaction between Sex and Stress exposure, onabsolute intake (g/kg) and on preference (percent of ethanol consumed): F(1,24)= 17,83;F(1,24)= 17,53; ps < 0,001, respectively. Stressed females exhibited higher levels of alcoholintake than control females. (Fig. 2). The opposite pattern was observed on males.Experiment 2 indicated that the facilitatory effects of stress on alcohol intake in female ratswas blockaded by nor-BNI (Fig. 3). Nor-BNI administered stressed females consumedsignificantly less alcohol than those that did not received nor-BNI: F(1,26)= 6.60; F(1,26)=5.09, ps < 0.05, for g/kg and percent of preference, respectively).Adolescents are vulnerable to the permissive effects of stress on alcohol intake. Exposureto adverse events may enhance the risk of exacerbated alcohol intake in adolescents. Apronounced sex-related difference in the response stress was observed, with femalesconsuming significantly more alcohol after stress exposure, when compared to untreatedcounterparts. The relationship found in females between stress and subsequent alcoholconsumption, guides to further analysis of the molecular basis underlying this permissiveeffects.