Indirect Modulation by α7 Nicotinic Acetylcholine Receptors of Noradrenaline Release in Rat Hippocampal Slices: Interaction with Glutamate and GABA Systems and Effect of Nicotine Withdrawal

Publisher Website
Google Scholar
Abstract
Nicotinic acetylcholine receptors (nAChRs) can modulate transmitter release. Striatal [3H]dopamine ([3H]DA) release is regulated by presynaptic nAChR on dopaminergic terminals and α7 nAChR on neighboring glutamatergic afferents. Here, we explored the role of α7 nAChR in the modulation of [3H]noradrenaline ([3H]NA) release from rat hippocampal slices. The nicotinic agonist anatoxin-a (AnTx) evoked monophasic [3H]NA release (EC50 = 1.2 μM) that was unaffected by α-conotoxin-MII or dihydro-β-erythroidine, antagonists of α3/α6β2* and β2* nAChR, respectively. In contrast AnTx-evoked striatal [3H]DA release was biphasic (EC50 = 138.9 nM; 7.1 μM) and blocked by these antagonists. At a high AnTx concentration (25 μM), α7 nAChR antagonists (methyllycaconitine, α-conotoxin-ImI) and glutamate receptor (GluR) antagonists [kynurenic acid, 6,7-dinitroquinoxaline-2,3-dione (DNQX)] partially inhibited [3H]NA release. The α7 nAChR-selective agonist choline evoked [3H]NA release (Emax = 33% of that of AnTx) that was blocked by GluR antagonists, supporting a model in which α7 nAChRs trigger glutamate release that subsequently stimulates [3H]NA release. A GABAergic component was also revealed: choline-evoked [3H]NA release was partially blocked by the GABAA receptor antagonist bicuculline, and coapplication of bicuculline and DNQX fully abolished this response. These findings support α7 nAChR on GABAergic neurons that can promote GABA release which, in turn, leads to [3H]NA release, probably by disinhibition. To investigate the impact of long-term nicotine exposure on this model, rats were exposed for 14 days to nicotine (4 mg/kg/day) with or without 3 or 7 days of withdrawal. α7 nAChR responses were selectively and transiently up-regulated after 3 days of withdrawal. This functional up-regulation could contribute to the withdrawal effects of nicotine.
Keywords

This publication has 43 references indexed in Scilit: