Reversal of chlorpromazine-induced avoidance depression by the N-methyl-d-aspartate antagonist, dizocilpine, in mice

Abstract

Abstract The non-competitive N-methyl-d-aspartate (NMDA) antagonist MK-801 (dizocilpine) was tested, alone or in combination with chlorpromazine, in mice previously trained in the shuttle-box. The lowest doses of dizocilpine (0·02 and 0·04 mg kg−1) attenuated the disrupting action of the neuroleptic (1·5 mg kg−1) on avoidance-performance, while avoidance depression induced by 1·5 and 2 mg kg−1 chlorpromazine was completely or almost completely reversed by 0·08 mg kg−1 NMDA antagonist. The highest dose (0·16 mg kg−1) of dizocilpine did not ameliorate avoidance-performance of mice receiving 2 mg kg−1 chlorpromazine, perhaps because of ataxic effects produced by the drug combination, at these doses. The results support suggestions for a potential use of NMDA antagonists in the treatment of extrapyramidal side-effects of neuroleptics.