Central effects of clozapine in regulating micturition in anesthetized rats

BACKGROUND We previously showed that systemic administration of the atypical neuroleptic clozapine in the rat altered a number of urodynamic variables and inhibited the external urethral sphincter. Since clozapine acts at several receptor types both at the periphery and the central nervous system, the site of action remained uncertain. Therefore, the purpose of this study was to determine the effects of central administration of clozapine on the bladder and the external urethral sphincter during cystometry and to examine differences in spinal versus supraspinal administration. We extended our observations by delivering clozapine centrally in anesthetized rats instrumented with either an intrathecal (L6-S1 spinal segment) or an intracerebroventricular (lateral ventricle) catheter. RESULTS Clozapine decreased micturition volume and increased residual volume possibly by acting at a supraspinal site. Expulsion time and amplitude of the high frequency oscillations were reduced by clozapine possibly by acting at a spinal site. Bladder capacity was increased after central clozapine but probably due to a peripheral effect. Clozapine acting at spinal and supraspinal sites increased pressure threshold. Contraction time and peak pressure were not affected by clozapine. The EMG from the external urethral sphincter was also reduced following clozapine centrally and suggests a spinal and a supraspinal site of action. CONCLUSIONS The results from the present study suggest that spinal and supraspinal central sites mediate clozapine's action in inhibiting expulsion parameters and the external urethral sphincter of the rat. Therefore, the reduction in the voiding efficiency observed after clozapine appears to be mediated by spinal and supraspinal sites.