Figure 7

Summary of the effects of clozapine given i.t., i.c.v. or i.v. (data from [12]) on urodynamic parameters and the activity of the EUS during cystometry in anesthetized rats. The first dose to yield a significant effect has been plotted for all 3 routes. Doses have been converted to mg/kg for ease of comparison. Peak pressure data are not shown since no significant differences were found with clozapine after any route. A) Bladder capacity is increased to a similar extent by comparable doses of clozapine, regardless of the route. Therefore, a peripheral effect may be predominating. In the case of micturition volume (B) and residual volume (C), both clearly show a central effect since the first dose to yield a significant effect is 142× smaller than the i.v. dose. Both of these parameters show a possible supraspinal site of action. D) Pressure threshold increased only after the highest dose of clozapine i.c.v or i.t., however, that dose was still 14× smaller than the first dose i.v., suggesting a possible central effect. E) Expulsion time shows a 142× difference between the central dose and the peripheral dose. In addition, intrathecal administration shows a larger effect than after i.c.v., suggesting a possible spinal site of action. F) The effect of clozapine on the amplitude of the HFO appears to be mediated by a spinal site. G) Phase 1 of the EMG was decreased after equivalent doses of clozapine i.v. or i.c.v. Intrathecal administration had no effect. H) Phase 2 of the EMG (where the bursting occurs) clearly showed a central effect since a much smaller dose (142×) was required to produce an effect. In addition, the reduction after i.c.v. was greater than after i.t. therefore suggesting a possible supraspinal site of action. I) Phase 3 of the EMG was not affected by clozapine intrathecally. Only the highest dose of clozapine given i.c.v decreased the EMG during this phase. That dose was 14× smaller than the first dose to produce a significant effect after i.v. administration suggesting a possible supraspinal site of action. J) The amplitude of the individual bursts during phase 2 of the EMG was decreased by central effects of clozapine at smaller doses than those observed i.v. Also, the intrathecal administration was much more effective in reducing the amplitude (abolished in 4/6) animals, suggesting a possible spinal site of action.