5-hydroxytryptamine 1a-likereceptor activation in the bed nucleus of the stria terminalis: Electrophysiological and behavioral studies

Abstract

The anteriorlateral bed nucleus of the stria terminalis (BNST AL) and the serotonergic system are believed to modulate behavioral responses to stressful and/or anxiogenic stimuli. However, although the BNST AL receives heavy serotonergic innervation, the functional significance of this input is not known. Data obtained from in vitro whole-cell patch clamp recording in the rat BNST slice show that exogenous application of 5-hydroxytryptamine (5-HT) evoked a heterogeneous response in BNST AL neurons. The principal action of 5-HT in this region was inhibitory, evoking a membrane hyperpolarization (5-HT Hyp) and a concomitant reduction in input resistance in the majority of neurons tested. The broad-spectrum 5-HT 1 agonist, 5-carboxamindotryptamine (5-CT), but not R(±)8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT), mimicked the 5-HT Hyp response in the BNST. Moreover, the outward current mediating 5-HT Hyp was inwardly rectifying and sensitive to the G protein activated inwardly rectifying K + (G IRK) channel blocker, tertiapin-Q. In the CNS 5-HT 1A receptors are thought to couple to G IRK channels, suggesting that 5-HT Hyp in BNST AL neurons was mediated by activation of 5-HT 1A-like receptors. This was confirmed by the blockade of both 5-HT Hyp and 5-CT Hyp by the specific 5-HT 1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]- N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY100635 200nM). Furthermore, an in vivo examination of the functional consequences of 5-HT 1A-like induced inhibition of BNST neurons revealed that infusion of 5-CT into the BNST significantly reduced the acoustic startle response, without affecting the general motor activity of the animals. These data point to the possibility that 5-HT 1A mediated inhibition of the BNST AL could contribute to an anxiolytic action. Hence, we propose that in response to stressful stimuli, enhanced levels of 5-HT in the BNST AL plays a critical homeostatic role in feedback inhibition of the anxiogenic response to these stimuli.