P.2.014 Study of the effects of aripiprazole and olanzapine on learning and memory in naive rats and rats with apomorphine-induced behavior

Abstract

Purpose: Aripiprazole is an atypical antipsychotic alternative for antipsychotic drugs that adversely affect cognitive processes [1]. The atypical antipsychotic olanzapine acts as a dopamine, serotonin and muscarinic antagonist, and its effect on these neurotransmitters could result in memory impairment in working memory tasks [2]. Apomorphine induces conditioning by stimulation of dopamine receptors [3]. Our aim was to assess the impact of aripiprazole and olanzapine on behavioral functions of rats, with particular emphasis on memory effects after multiple dosing. Methods: Two experiments were carried out using the active avoidance test. Experiment 1 (naive rats) comprised 6 groups of 8 male Wistar rats each, treated intraperitoneally (i.p.) with: (1) saline 0.1ml/100 g (control group); (2,3) aripiprazole 1mg/kg and 3mg/kg, respectively; (4,5,6) olanzapine 0.5mg/kg, 1mg/kg and 2mg/kg, respectively. Experiment 2 (apomorphine-challenged rats) comprised 4 groups of 8 male Wistar rats each, treated intraperitoneally (i.p.) with: (1) saline 0.1ml/100 g (control group); (2) apomorphine 0.5mg/kg; (3) apomorphine 0.5mg/kg plus aripiprazole 1mg/kg; (4) apomorphine 0.5mg/kg plus olanzapine 1mg/kg. Rats were trained in an automatic reflex conditioner (shuttle box) with 5 learning sessions on days 1−5 and a memory retention test on day 12. The following parameters were recorded: number of avoidances, number of escapes from foot shock and number of inter-trial crossings. Statistical evaluation was performed using ANOVA. Results: Of the naive rats, the control group significantly increased the number of avoidances both in learning sessions and in the memory retention test, compared to day 1. Rats treated with aripiprazole had lower numbers of avoidances than controls in all learning sessions and in the memory retention tests. Rats treated with olanzapine had lower numbers of avoidances than controls in the learning sessions on days 4 and 5 and in the memory retention test. In all of the naive rats, neither the number of escapes nor the number of inter-trial crossings changed during the learning sessions and the memory test. Of the rats challenged with apomorphine, those treated only with apomorphine had increased numbers of avoidances in the learning sessions and in memory retention test (p< 0.05). Rats treated with apomorphine plus aripiprazole had lower numbers of avoidances than apomorphine-only rats in the learning sessions on days 3, 4 and 5 and in the memory retention test (p< 0.05). Rats treated with apomorphine plus olanzapine had similar numbers of avoidances as apomorphine-only rats in the learning sessions, but lower numbers in the memory retention test (p< 0.05). The numbers of escapes and intertrial crossings showed a similar tendency. Conclusion: In these experiments, the antipsychotic drugs aripiprazole and olanzapine impaired learning and memory of apomorphine-naive rats in the active avoidance test. In apomorphine-challenged rats, aripiprazole antagonized the effects of apomorphine on both learning and memory, but olanzapine affected memory only. This suggests that aripiprazole and olanzapine modulate dopamine neurotransmission in different ways.