The effect of clozapine and GABAA receptor drugs on scopolamine‑induced amnesia in male mice

Abstract

Scopolamine, a muscarinic acetylcholine receptor antagonist, disturbs learning and memory processes. Clozapine, an atypical antipsychotic, has beneficial predictive validity for confirming principles to help new treatment approaches. It could improve the cognitive deficit. Furthermore, clozapine has affinity for the cholinergic and GABAergic receptors. This investigation examined the effects of clozapine and/or GABA_A receptor drugs on scopolamine‑induced memory impairment in male mice. Step‑down passive avoidance and open‑field tests were utilized for assessing memory acquisition and locomotor activity, respectively. The results exhibited that pre‑training administration of muscimol but not bicuculline induced amnesia without affecting locomotor activity. Moreover, pre‑training administration of clozapine did not significantly modify memory acquisition, but co‑administration of scopolamine and clozapine improved the amnesia produced with scopolamine. Also, co‑administration of muscimol along with clozapine potentiated memory impairment induced by scopolamine, whereas co‑injection of bicuculline along with clozapine reversed memory impairment produced by scopolamine. These treatments did not significantly change locomotor activity. Based on the findings, it is concluded that the GABAergic system modulates memory acquisition, and clozapine interacts with both muscarinic and GABAergic systems to bidirectionally regulate scopolamine‑induced amnesia. These results suggest the potential involvement of GABAergic mechanisms in the memory‑impairing effects of scopolamine and highlight the therapeutic potential of clozapine in mitigating cholinergic dysfunction‑related memory deficits.