5-HT1A and 5-HT2 receptors differentially regulate the excitability of 5-ht-containing neurones of the guinea pig dorsal raphe nucleus in vitro

• Published in: Brain research Vol. 899; no. 1-2; pp. 159 - 168
• Main Authors: CRAVEN, Rebecca M, GRAHAME-SMITH, David G, NEWBERRY, Nigel R
• Format: Journal Article
• Language: English
• Published: London Elsevier 27.04.2001; Amsterdam; New York, NY
• Subjects: Animals; Biological and medical sciences; Central nervous system; Electrophysiology; Fundamental and applied biological sciences. Psychology; Guinea Pigs; Male; Neurons - drug effects; Neurons - physiology; Potassium Channel Blockers; Potassium Channels - physiology; Raphe Nuclei - drug effects; Raphe Nuclei - physiology; Receptors, Serotonin - physiology; Receptors, Serotonin, 5-HT1; Serotonin - physiology; Serotonin Antagonists - pharmacology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Vertebrates: nervous system and sense organs; Vertebrata; Mammalia; Guinea pig; 5-HT1A Serotonine receptor; Rodentia; Central nervous system; Electrophysiology; Excitability; Raphe nucleus; 5-HT2 Serotonine receptor; Brain (vertebrata)
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/s0006-8993(01)02221-1

We have used intracellular recording techniques to examine the effects of 5-hydroxytryptamine (5-HT, serotonin) on 5-HT-containing neurones of the guinea pig dorsal raphe nucleus in vitro. Bath-applied 5-HT (30-300 microM) had two opposing effects on the membrane excitability of these cells, reflecting the activation of distinct 5-HT receptor subtypes. As demonstrated previously in the rat, 5-HT evoked a hyperpolarization and inhibition of 5-HT neurones, which appeared to involve the activation of an inwardly rectifying K(+) conductance. This hyperpolarizing response was blocked by the 5-HT(1A) receptor-selective antagonist WAY-100635 (30-100 nM). In the presence of WAY-100635, 5-HT induced a previously unreported depolarizing, excitatory response of these cells, which was often associated with an increase in the apparent input resistance of the neurone, likely due to the suppression of a K(+) conductance. Like the hyperpolarizing response to 5-HT, this depolarization could be recorded in the presence of the Na(+) channel blocker tetrodotoxin. In addition, the response was not significantly attenuated by the alpha(1)-adrenoceptor antagonist prazosin (500 nM), indicating that it is not due to the release of noradrenaline, or to the direct activation of alpha(1)-adrenoceptors by 5-HT. The 5-HT(3) receptor antagonist granisetron (1 microM) and the 5-HT(4) receptor antagonist SB 204070 (100 nM) failed to reduce the depolarizing response to 5-HT; however, ketanserin (100 nM), mesulergine (100 nM) and lysergic acid diethylamide (1 microM) significantly reduced or abolished the depolarization, indicating that this effect of 5-HT is mediated by 5-HT(2) receptors.