Figure 1

Representative traces of the effects of increasing dose of clozapine administered intrathecally (over the L6/S1 spinal segments) on the cystometrogram and external urethral sphincter of anesthetized rats (n = 6). Top panel shows bladder pressure during filling (0.11 ml/min) while bottom panel shows the integrated EMG recorded from the external urethral sphincter. Panels A and B also show some of the urodynamic parameters measured during cystometry: BC = amount of fluid infused into the bladder to elicit a contraction; PT = pressure at which contraction begins; PP = peak pressure during contraction; CT = contraction time; HFO = high frequency oscillations recorded during expulsion; ET = time between peak pressure and end of high frequency oscillations. The EMG activity was examined by dividing the contraction into 3 phases [19]: a contraction phase (Phase 1); an expulsion phase (Phase 2); a closing phase (Phase 3). A) Cystometrogram (CMG) following administration of vehicle (saline) intrathecally. (B) Expanded time scale shows the HFO and the concomitant bursting pattern in the EUS EMG. C & D) 0.5 nmoles of clozapine i.t. does not have an effect on the CMG or the EUS EMG. E & F) 5 nmoles of clozapine i.t. abolished the HFO (4/6 rats) and the bursting pattern in the EUS EMG. G & H) 50 nmoles of clozapine i.t. increased the bladder capacity and also abolished the HFO and the bursting pattern in the EUS EMG of some rats (2/6). Unstable, non-voiding contractions were occasionally seen following clozapine administration and preceding the final voiding contraction (1C; 1G). Calibration bar: A,C,E,G = 1 min; B,D,F,H = 1 sec.