PMID- 15381287 OWN - NLM STAT- MEDLINE DCOM- 20050304 LR - 20141120 IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 128 IP - 3 DP - 2004 TI - 5-hydroxytryptamine1A-like receptor activation in the bed nucleus of the stria terminalis: electrophysiological and behavioral studies. PG - 583-96 AB - 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-HTHyp) and a concomitant reduction in input resistance in the majority of neurons tested. The broad-spectrum 5-HT1 agonist, 5-carboxamindotryptamine (5-CT), but not R(+/-)8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT), mimicked the 5-HTHyp response in the BNST. Moreover, the outward current mediating 5-HTHyp was inwardly rectifying and sensitive to the G protein activated inwardly rectifying K+ (G IRK) channel blocker, tertiapin-Q. In the CNS 5-HT1A receptors are thought to couple to GIRK channels, suggesting that 5-HTHyp in BNST AL neurons was mediated by activation of 5-HT1A-like receptors. This was confirmed by the blockade of both 5-HTHyp and 5-CTHyp by the specific 5-HT1A 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-HT1A-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-HT1A 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. FAU - Levita, L AU - Levita L AD - Department of Psychiatry and Behavioral Neuroscience, Emory University, Yerkes Neuroscience Building, 954 Gatewood Drive, Room 5220, Atlanta, GA 30322, USA. FAU - Hammack, S E AU - Hammack SE FAU - Mania, I AU - Mania I FAU - Li, X-Y AU - Li XY FAU - Davis, M AU - Davis M FAU - Rainnie, D G AU - Rainnie DG LA - eng GR - MH 57250/MH/NIMH NIH HHS/United States GR - MH47840/MH/NIMH NIH HHS/United States GR - MH59906/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (G Protein-Coupled Inwardly-Rectifying Potassium Channels) RN - 0 (Potassium Channel Blockers) RN - 0 (Potassium Channels, Inwardly Rectifying) RN - 0 (Serotonin 5-HT1 Receptor Agonists) RN - 0 (Serotonin Antagonists) RN - 0 (Serotonin Receptor Agonists) RN - 112692-38-3 (Receptor, Serotonin, 5-HT1A) RN - 333DO1RDJY (Serotonin) SB - IM MH - Afferent Pathways/drug effects/*metabolism MH - Animals MH - G Protein-Coupled Inwardly-Rectifying Potassium Channels MH - Male MH - Membrane Potentials/drug effects/physiology MH - Neural Inhibition/drug effects/physiology MH - Neurons/drug effects/*metabolism MH - Organ Culture Techniques MH - Patch-Clamp Techniques MH - Potassium Channel Blockers/pharmacology MH - Potassium Channels, Inwardly Rectifying/drug effects/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, Serotonin, 5-HT1A/*metabolism MH - Reflex, Startle/drug effects/physiology MH - Septal Nuclei/drug effects/*metabolism MH - Serotonin/*metabolism/pharmacology MH - Serotonin 5-HT1 Receptor Agonists MH - Serotonin Antagonists/pharmacology MH - Serotonin Receptor Agonists/pharmacology EDAT- 2004/09/24 05:00 MHDA- 2005/03/05 09:00 CRDT- 2004/09/24 05:00 PHST- 2004/06/23 00:00 [accepted] PHST- 2004/09/24 05:00 [pubmed] PHST- 2005/03/05 09:00 [medline] PHST- 2004/09/24 05:00 [entrez] AID - S0306-4522(04)00532-9 [pii] AID - 10.1016/j.neuroscience.2004.06.037 [doi] PST - ppublish SO - Neuroscience. 2004;128(3):583-96. doi: 10.1016/j.neuroscience.2004.06.037.