A Neuropsychological Assessment of the Effects of Chronic Ketamine Exposure in a Rodent Model of Drug Abuse

Abstract

While used as paediatric and veterinary anaesthetic and for pain management, the nonselective NMDA (N-methyl-D- aspartate) antagonist ketamine also remains popular among recreational users. As such, there is legitimate concern about the psychological and physiological consequences associated with chronic abuse of this drug. The purpose of the present investigation was to assess the impact of chronic exposure to ketamine following a period of abstinence in a rodent model of ketamine abuse. In the present experiment, rats were given repeated injections of saline, 5 mg/kg, or 40 mg/kg of ketamine. Beginning at 111 days of age, the animals were tested for retention of an aversive outcome on a step-down avoidance task and assessed for general levels of activity. In addition, the animals were trained on a series of tasks with spatial components of various levels of difficulty, a spatial learning set task, and a nonspatial response learning task. On early trials with water maze tasks of varying difficulty, the ketamine-treated rats were impaired relative to controls, with dose-dependent effects observed on many of the tasks. On probe trials the drug-treated animals spent significantly less time in the target quadrant. In addition, the performance of the drug-treated rats was inferior to that of the control animals on a spatial learning set task, and a response learning task suggesting some difficulty in adapting their responses to changing task demands. The results suggest that chronic exposure to this NMDA receptor antagonist in young adult rats is capable of producing a variety of changes that affect nonspatial learning and memory performance in adulthood, well after the drug exposure period.