Dados do Trabalho

Título

EFFECTS OF REPEATED AND COMBINED TREATMENT OF TOPIRAMATE AND ARIPIPRAZOLE ON THE ETHANOL-INDUCED CONDITIONED PLACE PREFERENCE IN FEMALE MICE

Fundamentação/Introdução

Alcohol is one of the most widely used psychoactive substances in the world, which acts by modulating the GABAergic, glutamatergic and dopaminergic systems to produce dependence behaviors, but effective pharmacological therapies for alcoholism are still limited.

Objetivos

The aim of this study was to verify the effect of combined and repeated treatment of topiramate (TOP), an anticonvulsant drug glutamatergic antagonist that facilitates the effects of GABA, and aripiprazole (ARP), that acts mainly as a partial agonist of D2 receptors and 5 -HT1A, of ethanol-induced conditioned place preference (CPP).

Delineamento e Métodos

Thus, 3-month-old female Swiss mice were submitted to a preconditioning test followed by conditioning with saline (Sal) on odd days and 1.8 mg/kg ethanol (ip.) on even days during 8 daily sessions and CPP was quantified on a post-conditioning session (CEUA-UESC nº 005/16). Then the reconditioning phase was started, where the animals were treated with saline (Sal) in the CPP compartment previously associated with Sal on odd days or TOP (2.5, 5.0 or 10 mg/kg - Experiment (EXP) 1) or ARP (0.025, 0.05, 0.075 or 0.1 mg/kg - EXP2) or TOP + ARP (5.0 mg/kg and 0.075 mg/kg - EXP3, respectively) in the CPP compartment previously associated with ethanol on even days during 8 daily sessions. Forty-eight hours later animals were re-exposed to ethanol (1.8mg/kg) and CPP was quantified on the next day.

Resultados

The results demonstrated that individual treatment with TOP10 (294.7±30.87) and ARP0.1 (303.7±32.02) can block the expression of CPP when compared to the vehicles (EXP1 452.1±42.51; EXP2 410.2±19.97). The combination of less effective doses of this drugs TOP5.0 + ARP0.075 (309.1±33.11) also prevented the expression of CPP when compared to the VEI (432.1±48.23) [Two-way Anova/Bonferroni post hoc - p <0.05].

Conclusões/Considerações Finais

Thus, our results suggest that topiramate and aripiprazole reduces the rewarding properties of ethanol, proposing combination therapy as a therapeutic alternative of dependence. This summary was presented at SBNeC 2018.

Palavras-chave

Dependence, conditioned place preference, ethanol, topiramate, aripiprazole.