Memantine improves memory impairment and depressive-like behavior induced by amphetamine withdrawal in rats

Amphetamine (AMPH) induces deficits in cognition, and depressive-like behavior following withdrawal. The aim of the present study was to investigate whether pre-treatment with memantine (5mg/kg, i.p.), a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, attenuates memory impairment induced by withdrawal from a 1 day binge regimen of AMPH (2mg/kg, four times every 2h, i.p.), in the novel object recognition test in rats. Herein, the influence of scopolamine (0.1mg/kg), an antagonist of the muscarinic cholinergic receptors, and the impact of MK-801 (0.1mg/kg), an antagonist of the NMDA receptors, on the memantine effect, were ascertained. Furthermore, the impact of memantine (5; 10; 20mg/kg, i.p.) was measured on depression-like effects of abstinence, 14 days after the last AMPH treatment (2mg/kg×1×14 days), in the forced swim test. In this test, the efficacy of memantine was compared to that of tricyclic antidepressant imipramine (10; 20; 30mg/kg, i.p.). Our study indicated that withdrawal from a binge regimen of AMPH impaired recognition memory. This effect was attenuated by administration of memantine at both 72h and 7 days of withdrawal. Moreover, prior administration of scopolamine, but not MK-801, decreased the memantine-induced recognition memory improvement. In addition, memantine reversed the AMPH-induced depressive-like behavior in the forced swim test in rats. The antidepressant-like effects of memantine were stronger than those of imipramine. Our study indicates that memantine constitutes a useful approach towards preventing cognitive deficits induced by withdrawal from an AMPH binge regimen and by depressive-like behavior during AMPH abstinence.