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

Neuroscience. 2004;128(3):583-96. doi: 10.1016/j.neuroscience.2004.06.037.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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


  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Potassium Channel Blockers
  • Potassium Channels, Inwardly Rectifying
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Receptor, Serotonin, 5-HT1A
  • Serotonin