Interaction between D2 dopaminergic and glutamatergic excitatory influences on lower urinary tract function in normal and cerebral-infarcted rats

Previous studies showed that bladder hyperactivity after cerebral infarctio n in Sprague-Dawley (SD) rats was mediated in part by D2 dopaminergic and N MDA glutamatergic mechanisms. In the present experiments, the interaction b etween dopaminergic and glutamatergic excitatory mechanisms in the control of bladder and external urethral sphincter (EUS) reflexes was investigated in urethane-anesthetized sham-operated (SO) and cerebral-infarcted (CI) SD rats. Occlusion of the left middle cerebral artery or a sham operation was performed under halothane anesthesia. Two hours after either of the two pro cedures, rats were anesthetized with urethane. Dizocilpine, an N-methyl-D-a spartate (NMDA) glutamatergic antagonist, was administered intravenously in doses of 0.3 or 3 mg/kg to CI rats and 3 mg/kg to SO rats. These doses com pletely inhibited bladder and EUS activity. The effects of apomorphine (a d opamine agonist with greater efficacy at D2 than D1 receptors) or quinpirol e (a selective D2 dopamine receptor agonist) were examined on the dizocilpi ne-induced depression of bladder contractions and EUS EMG activity. Apomorp hine did not antagonize the dizocilpine depression of EUS activity, but it did reestablish the micturition reflex after dizocilpine blockade and did i ncrease the amplitude of bladder contractions and voided volume in a dose-d ependent manner (0.0001-10 mg/kg, iv), in both CI rats and SO rats pretreat ed with dizocilpine. There were no differences between SO rats and CI rats in the apomorphine responses in rats pretreated with doses of 0.3 or 3 mg/k g dizocilpine. A larger dose of dizocilpine (10 mg/kg) did not affect the b ladder contractions after apomorphine administration. Quinpirole (0.001-1 m g/kg, iv) also partially reversed the dizocilpine depression of bladder act ivity in SO and CI rats. These results indicate that NMDA glutamatergic and D2 dopaminergic mechanisms exert independent excitatory influences on blad der activity in both SO and CI rats. D2 dopamine receptor agonists can reve rse the effect of NMDA receptor blockade on bladder activity but were ineff ective in reversing the block of sphincter activity. (C) 2001 Academic Pres s.