Evaluation of the antidepressant, anxiolytic and memory-improving efficacy of aripiprazole and fluoxetine in ethanol-treated rats.
Some study results indicate a positive effect of aripiprazole (ARI) on impaired cognitive functions caused by brain damage resulting from chronic EtOH abuse. However, other research shows that to manifest itself, an ARI antidepressant effect requires a combined therapy with another selective serotonin reuptake inhibitor antidepressant, namely, fluoxetine (FLX). The aim of this article was to assess antidepressant and anxiolytic effects of ARI as well as its effect on spatial memory in ethanol-treated (alcoholized) rats. On the basis of alcohol consumption pattern, groups of (1) ethanol-preferring rats, with mean ethanol intake above 50%, and (2) ethanol-nonpreferring rats (EtNPRs), with mean ethanol intake below 50% of total daily fluid intake, were formed. The group of EtNPRs was used for this study, subdivided further into three groups administered ARI, FLX and a combination of both, respectively. Behavioral tests such as Porsolt's forced swimming test, the Morris water maze test and the two-compartment exploratory test were employed. Behavioral test results demonstrated (1) no antidepressant effect of ARI in EtNPRs in subchronic treatment and (2) no procognitive effect of ARI and FLX in EtNPRs in combined single administration. Combined administration of both drugs led to an anxiogenic effect and spatial memory deterioration in study animals. ARI had no antidepressant effect and failed to improve spatial memory in rats. However, potential antidepressant, anxiolytic and procognitive properties of the drug resulting from its mechanism of action encourage further research aimed at developing a dose of both ARI and FLX that will prove such effects in alcoholized EtNPRs.
Department of Pharmacoeconomics and Social Pharmacy, University of Medical Sciences in Poznań , Poznań , Poland.
Kinga
K
Burda-Malarz
Krzysztof
K
Kus
Piotr
P
Ratajczak
Anna
A
Czubak
Szymon
S
Hardyk
Elżbieta
E
Nowakowska
D000437:Alcoholism / Q000188:drug therapy*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000068180:Aripiprazole; D001522:Behavior, Animal / Q000187:drug effects; D004359:Drug Therapy, Combination; D000431:Ethanol / Q000633:toxicity*; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D015363:Quinolones / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D065852:Spatial Memory / Q000187:drug effects; D013550:Swimming
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D000068180:Aripiprazole; D000431:Ethanol; D005473:Fluoxetine; D010879:Piperazines; D015363:Quinolones; D017367:Selective Serotonin Reuptake Inhibitors
Atypical antipsychotic; cognitive function; ethanol dependence