THE DISRUPTIVE EFFECTS OF KETAMINE ON PASSIVE-AVOIDANCE LEARNING IN MICE - INVOLVEMENT OF DOPAMINERGIC MECHANISM

The involvement of dopaminergic mechanisms in ketamine-induced disruption of one trial step-through passive avoidance performance was assessed through the coadministration with the dopamine D-1 antagonist SCH 23390, the dopamine D-2 antagonist YM-091512 and the dopamine autoreceptor agonist at low doses, apomorphine, in mice. Pretraining (10 min before) administration of ketamine (0; saline, 2.5, 5 and 10 mg/kg SC) dose-dependently reduced the latency in the retention trial conducted 24 h after the training. However, ketamine did not affect the retention latency when administered immediately after the training or prior to retention. YM-09151-2 (0.01 and 0.03 mg/kg SC) and apomorphine (0.01 and 0.03 mg/kg SC), but not SCH 23390 (0.01 and 0.03 mg/kg SC), ameliorated the impaired reduction by ketamine (10 mg/kg) in a dose-dependent manner. These results suggest that ketamine obstructs the acquisition of the passive avoidance task, and that this effect is induced by stimulation of dopamine D-2 receptors through dopamine release from the presynaptic terminals.