Clozapine improves dizocilpine-induced delayed alteration impairment in rats

The effects of systemic administration of dizocilpine (0.16 mg/kg, i.p.), clozapine (7.5 mg/kg, s.c.) and coadministration of dizocilpine (0.16 mg/kg, i.p.) and clozapine (7.5 mg/kg, s.c.) on acquisition of delayed alternation in a T-maze were tested in rats (N = 7 per group) on six days with 10 choices per day and animal. Clozapine given alone did not impair delayed alternation learning, except of the first day. Dizocilpine induced a significant delayed alternation impairment on all days tested. Pretreatment with clozapine significantly improved the dizocilpine-induced impairment. Treatment-induced changes of delayed alternation learning and of locomotor activities showed no correlation. The results demonstrate that clozapine functionally compensated for deficits induced by a blockade of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors.