Bradycardic responses to microinjection of N-methyl-D-aspartate into the nucleus tractus solitarius are inhibited by local activation of 5-HT3 receptors

Previous reports have described that glutamate ionotropic receptors in the nucleus tractus solitarius (NTS) are involved in the reflex control of hear t rate, and that such a control can be inhibited by NTS-5-HT3 receptor stim ulation. In the present study, we examined in urethane anaesthetized rats t he effects of intra-NTS microinjection of 1-(m-chlorophenyl)-biguanide (CPB G), a potent and selective 5-HT3 receptor agonist, on the cardiovascular re sponses to local administration of glutamate ionotropic receptor agonists. Intra-NTS microinjection of CPBG reduced the atropine-sensitive bradycardia elicited by local microinjection of NMDA without affecting the cardiovascu lar responses to intra-NTS microinjections of AMPA or kainic acid. The redu ction by CPBG of the NMDA-evoked cardiac response was blocked by prior intr a-NTS microinjection of granisetron, a 5-HT3 receptor antagonist, as well a s bicuculline, a GABA(A) receptor antagonist. These results suggest that th e stimulation of NTS 5-HT3 receptors specifically reduces, via a GABA-depen dent mechanism, the cardiac response to local NMDA administration. (C) 2000 Elsevier Science Ltd. All rights reserved.