Suppression of the rat micturition reflex by imipramine

1. This study investigates possible mechanisms through which imipramine (IMI) exerts its antienuretic effect. The micturition reflex in response to bladder distension produced by saline infusion was examined in anaesthetized rats. 2. The amplitude and frequency of micturition reflex contractions were reduced by peripheral administration of IMI, but the micturition reflex was abolished after its intracerebroventricular (i.c.v.) administration. A muscarinic antagonist, atropine, displayed an inhibitory effect similar to that of IMI. A muscarinic agonist, carbachol, produced a dose-related rightward shift of the dose-response curve to IMI. Both IMI i.c.v. and the muscarinic antagonist l-methylscopolamine i.c.v. elevated the threshold of volume and pressure for micturition initiation, indicating that IMI and muscarinic antagonists mainly exert a central inhibitory effect on the micturition reflex. 3. In addition, to evaluate the role of central monoaminergic neurotransmission on micturition, the acetylcholine depletor hemicholinium-3 (HC-3), the catecholamines depletor alpha-methyl-p-tyrosine (AMPT), and the serotonin depletor p-chlorophenylalanine (PCPA) were examined alone or in combination with IMI. The micturition threshold was increased by treatment with HC-3, but not by AMPT or PCPA. In HC-3 treated rats, the inhibitory effect of IMI on the micturition reflex was more prolonged than in normal rats. After administration of IMI, the recovery from the cessation of micturition reflex contractions was facilitated by carbachol in normal rats, but not in HC-3 treated rats. This indicates that acetylcholine plays a facilitatory role in initiating micturition reflex contractions. 4. Acute treatment with IMI decreased the frequency and increased the volume threshold of micturition reflex contraction. Acute and chronic treatment with IMI prolonged the cessation period of micturition by IMI. 5. These results suggest that IMI exerts an inhibitory action on the micturition reflex by a central cholinergic mechanism. Muscarinic receptors located at the supraspinal level are tonically stimulated during distension-induced micturition reflex.