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J Neural Transm Gen Sect. 1992;89(1-2):1-10.

Typical and atypical neuroleptics antagonize MK-801-induced locomotion and stereotypy in rats.

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Neurogen Corporation, Branford, CT.


The effects of typical and atypical neuroleptics on MK-801-induced locomotor activity and stereotyped sniffing were tested. Pretreatment with the typical neuroleptic haloperidol (0.01, 0.05, 0.1, 0.5 mg/kg SC) and the dopamine D2 receptor selective antagonist eticlopride (0.005, 0.01, 0.05 mg/kg SC) each resulted in significant and dose-dependent reductions of locomotor activity and sniffing. The atypical neuroleptic clozapine (1.0, 5.0, 10.0 mg/kg SC) was somewhat unique in that all doses reduced locomotor activity, but only the highest dose (10.0 mg/kg) significantly reduced sniffing. The data support a functional interaction between glutamate and dopamine systems, and suggest that the behavioral activation associated with MK-801 may represent a valid model for detecting potential therapeutic agents in the treatment of schizophrenia. The data should be viewed as preliminary, however, until neuroleptics are characterized in other glutamate-based models that minimized or exclude the possible influence of nonspecific motor effects.

[Indexed for MEDLINE]

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