Contrasting effects of acute and chronic treatments with ketamine on inhibitory avoidance and escape latency in the elevated-t-maze

Abstract

Previous studies have suggested the involvement of N-Methyl,D-Aspartate (NMDA) pathway in the Pathophysiology of anxiety disorder. However the role of NMDA neurotransmission in the neurobiology of different classes of anxiety disorder remains unexplored. This study examined the effects of intraperitoneal administration of acute (3 mg/kg) and withdrawal from chronic administration of non-competitive NMDA receptor antagonist - ketamine (15 mg/kg daily for 21 days and withdrawn for 24 hours) on inhibitory avoidance duration (conditioned fear related behaviour) and escape latency (unconditioned fear related behaviour) using the elevated-T-maze (ETM) in mice (n = 10). The results showed that acute ketamine reduced while withdrawal from chronic ketamine administration increased inhibitory avoidance duration significantly (p < 0.05). Acute ketamine also increased escape latency, but withdrawal from chronic ketamine reduced escape latency significantly (p < 0.05). It was inferred that acute ketamine decreased conditioned and unconditioned fear related behaviours as a result of NMDA transmission downregulation, while withdrawal from chronic ketamine induced increase in conditioned and unconditioned related behaviours via NMDA transmission upregulation. Changes in NMDA transmission appear to be relevant in the neurobiology of generalized anxiety disorder and panic disorder related behaviours in the ETM, hence pharmacological modulation of NMDA transmission may contribute to improved treatment of generalised anxiety and panic disorders.

Keywords : N-Methyl,D-Aspartate, upregulation, downregulation, neurotransmission.