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Differential Effects of Haloperidol and Clozapine on Motor Recovery after Sensorimotor Cortex Injury in Rats

Department of Medicine (Neurology), Department of Veterans Affairs Medical Center, Durham, North Carolina; and the Department of Medicine (Division of Neurology), Duke Center for Cerebrovascular Disease, Center for Clinical Health Policy Research, Duke University, Durham, North Carolina, golds004{at}mc.duke.edu

Sarah Bullman

Department of Medicine (Neurology), Department of Veterans Affairs Medical Center, Durham, North Carolina; and the Department of Medicine (Division of Neurology), Duke Center for Cerebrovascular Disease, Center for Clinical Health Policy Research, Duke University, Durham, North Carolina

Background. A variety of drugs impair motor recovery after sensorimotor cortex (SMCTX) injury in laboratory animals and may have similar effects in humans. Methods. Rats (n = 142) underwent unilateral suction-ablation of the hindlimb SMCTX or sham lesion. After 24 hours, rats were given a single dose of placebo, haloperidol (0.1, 1.0, or 10.0 mg/kg, intraperitoneal), or clozapine (0.1, 0.5, 1.0, or 10.0 mg/kg, intraperitoneal), and motor recovery was measured. Results. Neither haloperidol (analysis of variance [ANOVA] F[3, 12], P = 0.43) nor clozapine (ANOVA F[4, 19], P = 1.00) affected motor performance in controls. Haloperidol impaired motor recovery (ANOVA F[3, 42], P = 0.002) at each tested dose, with no differences among the doses. The effect persisted after 2 weeks. In contrast, although rats given a single dose of clozapine of 1.0 or 10.0 mg/kg had poorer recoveries (ANOVA F[4, 51], P = 0.014), only those given the highest dose differed from controls. The effect was no longer apparent after 2 weeks. Conclusion. Consistent with previous reports, haloperidol retards motor recovery after SMCTX injury in rats. In contrast, there was no detrimental effect of clozapine when given at low doses. The use of low doses of atypical antipsychotics such as clozapine may provide a safer alternative to haloperidol in the treatment of agitated stroke patients.

Key Words: Haloperidol • Clozapine • Motor function • Cortex injury • Recovery

Neurorehabilitation and Neural Repair, Vol. 16, No. 4, 321-325 (2002)
DOI: 10.1177/154596830201600402


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