5-hydroxytryptamine1A-like receptor activation in the bed nucleus of the stria terminalis: electrophysiological and behavioral studies

L Levita, S E Hammack, I Mania, X-Y Li, M Davis, D G Rainnie

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)583-96
Number of pages14
Issue number3
Publication statusPublished - 2004


  • Afferent Pathways
  • Animals
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Male
  • Membrane Potentials
  • Neural Inhibition
  • Neurons
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Potassium Channel Blockers
  • Potassium Channels, Inwardly Rectifying
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1A
  • Septal Nuclei
  • Serotonin
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Startle Reaction

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