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 respo nse to bladder distension produced by saline infusion was examined in anaesthetized rats. 2 The amplitude and frequency of micturition refle x contractions were reduced by peripheral administration of IMI, but t he 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, car bachol, produced a dose-related rightward shift of the dose-response c urve to IMI. Both IMI i.c.v. and the muscarinic antagonist l-methylsco polamine i.c.v. elevated the threshold of volume and pressure for mict urition initiation, indicating that IMI and muscarinic antagonists mai nly exert a central inhibitory effect on the micturition reflex. 3 In addition, to evaluate the role of central monoaminergic neurotransmiss ion on micturition, the acetylcholine depletor hemicholinium-3 (HC-3), the catecholamines depletor alpha-methyl-p-tyrosine (AMPT), and the s erotonin depletor 9-chlorophenylalanine (PCPA) were examined alone or in combination with IMI. The micturition threshold was increased by tr eatment 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 th e cessation of micturition reflex contractions was facilitated by carb achol in normal rats, but not in HC-3 treated rats. This indicates tha t acetylcholine plays a facilitatory role in initiating micturition re flex 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 inhibi tory action on the micturition reflex by a central cholinergic mechani sm. Muscarinic receptors located at the supraspinal level are tonicall y stimulated during distension-induced micturition reflex.