Stimulation of brain α7-nicotinic acetylcholine receptors suppresses the rat micturition through brain GABAergic receptors

Brain nicotinic acetylcholine receptors (nAChRs) reportedly suppress the micturition, but the mecha-nisms responsible for this suppression remain unclear. We previously reported that intra-cerebroventricularly administered (+/-)-epibatidine (non-selective nAChR agonist) activated the sympatho-adrenomedullary system, which can affect the micturition. Therefore, we investigated (1) whether intracerebroventricularly administered (+/-)-epibatidine-induced effects on the micturition were dependent on the sympatho-adrenomedullary system, and (2) brain nAChR subtypes involved in the (+/-)-epibatidine-induced effects in urethane-anesthetized male Wistar rats. Plasma noradrenaline and adrenaline (catecholamines) were measured just before and 5 min after (+/-)-epibatidine administration. Evaluation of urodynamic parameters, intercontraction intervals (ICI) and maximal voiding pressure (MVP) by cystometry was started 1 h before (+/-)-epibatidine administration or intra-cerebroventricular pretreatment with other drugs and continued 1 h after (+/-)-epibatidine administration. Intra-cerebroventricularly administered (+/-)-epibatidine elevated plasma catecholamines and prolonged ICI without affecting MVP, and these changes were suppressed by intracerebroventricularly pretreated mecamylamine (non-selective nAChR antagonist). Acute bilateral adrenalectomy abolished the (+/-)-epi-batidine-induced elevation of plasma catecholamines, but had no effect on the (+/-)-epibatidine-induced ICI prolongation. The latter was suppressed by intracerebroventricularly pretreated methyllycaconitine (selective alpha 7-nAChR antagonist), SR95531 (GABA(A) antagonist), and SCH50911 (GABA(B) antagonist), but not by dihydro-beta-erythroidine (selective alpha 4 beta 2-nAChR antagonist). Intracerebroventricularly adminis-tered PHA568487 (selective alpha 7-nAChR agonist) prolonged ICI without affecting MVP, similar to (+/-)-epibatidine. These results suggest that stimulation of brain alpha 7-nAChRs suppresses the rat micturition through brain GABA(A)/GABA(B) receptors, independently of the sympatho-adrenomedullary outflow modulation. (C) 2021 Elsevier Inc. All rights reserved.

Automated summary

This study demonstrates that stimulation of brain alpha 7-nAChR receptors can suppress rat micturition through brain GABA receptors, independently of the sympatho-adrenomedullary system modulation.