The effect of 4-aminopyridine on micturition reflex in normal or capsaicin-desensitized rats

Abstract

4-aminopyridine (4-AP) produced a dose-related (0.15–2 mg/kg i.v.) potentiation of the voiding cycle of the urinary bladder and increased frequency of micturition in urethane-anesthetized rats. In bladders containing a subthreshold amount of fluid for eliciting reflex micturition 4-AP (1–3 mg/kg i.v.) activated a series of high-amplitude, hexamethonium-sensitive rhythmic bladder contractions. In rats desensitized to capsaicin as newborns, reflex micturition was almost abolished: in these animals i.v. 4-AP did not affect bladder voiding unless at high doses (1–2 mg/kg), at which a reversal from anesthesia occurred. This was accompanied by a prompt micturition. In unanesthetized rats, neither the 4-AP-induced convulsions nor the behavioral response (assessed in an open field) to 4-AP were affected by neonatal capsaicin desensitization. Daily urine production of capsaicin-pretreated animals did not differ from that of controls. However, when measurements were made during daytime, almost no spontaneous urine emission was found in capsaicin-treated rats. On the rat isolated urinary bladder, 4-AP potentiated the response to field stimulation in preparations from both vehicle- and capsaicin-pretreated animals. These findings indicate that 4-AP has a potent excitatory action on bladder voiding in rats and support the hypothesis that in this species ‘conscious’ bladder voiding can be initiated through capsaicin-resistant mechanisms.