1. Serotonin 5-HT2 receptors activate local GABA inhibitory inputs to serotonergic neurons of the dorsal raphe nucleus
- Author
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Rong-Jian Liu, Thierry Jolas, and George K. Aghajanian
- Subjects
Male ,Serotonin ,medicine.medical_specialty ,Interneuron ,Pyridines ,medicine.drug_class ,In Vitro Techniques ,Biology ,Inhibitory postsynaptic potential ,Piperazines ,Dorsal raphe nucleus ,Internal medicine ,medicine ,Animals ,Molecular Biology ,gamma-Aminobutyric Acid ,Neurons ,Afferent Pathways ,General Neuroscience ,Neural Inhibition ,Enkephalin, Ala(2)-MePhe(4)-Gly(5) ,Bicuculline ,Receptor antagonist ,Rats ,Serotonin Receptor Agonists ,Analgesics, Opioid ,Electrophysiology ,Indophenol ,medicine.anatomical_structure ,Endocrinology ,Receptors, Serotonin ,Raphe Nuclei ,GABAergic ,Serotonin Antagonists ,Neurology (clinical) ,Raphe nuclei ,Neuroscience ,Developmental Biology ,medicine.drug - Abstract
The purpose of the present study was to characterize the synaptic currents induced by bath-applied serotonin (5-HT) in 5-HT cells of the dorsal raphe nucleus (DRN) and to determine which 5-HT receptor subtypes mediate these effects. In rat brain slices, 5-HT induced a concentration-dependent increase in the frequency of inhibitory postsynaptic currents (IPSCs) in 5-HT neurons recorded intracellularly in the ventral part of the DRN (EC(50): 86 microM); 5-HT also increased IPSC amplitude. These effects were blocked by the GABA(A) receptor antagonist, bicuculline (10 microM) and by the fast sodium channel blocker, TTX, suggesting that 5-HT had increased impulse flow in local GABAergic neurons. DAMGO (300 nM), a selective mu-agonist, markedly suppressed the increase in IPSC frequency induced by 5-HT (100 microM) in the DRN. A near maximal concentration of the selective 5-HT(2A) antagonist, MDL100,907 (30 nM), produced a large reduction ( approximately 70%) in the increase in IPSC frequency induced by 100 microM 5-HT; SB242,084 (30 nM), a selective 5-HT(2C) antagonist, was less effective ( approximately 24% reduction). Combined drug application suppressed the increase in 5-HT-induced IPSC frequency almost completely, suggesting involvement of both 5-HT(2A) and 5-HT(2C) receptors. Unexpectedly, the phenethylamine hallucinogen, DOI, a partial agonist at 5-HT(2A/2C) receptors, caused a greater increase (+334%) in IPSC frequency than did 5-HT 100 microM (+80%). This result may be explained by an opposing 5-HT(1A) inhibitory effect since the selective 5-HT(1A) antagonist, WAY-100635, enhanced the 5-HT-induced increase in IPSCs. These results indicate that within the DRN-PAG area there may be a negative feedback loop in which 5-HT induces an increase in IPSC frequency in 5-HT cells by exciting GABAergic interneurons in the DRN via 5-HT(2A) and, to a lesser extent, 5-HT(2C) receptors. Increased GABA tone may explain the previous observation of an indirect suppression of firing of a subpopulation of 5-HT cells in the DRN induced by phenethylamine hallucinogens in vivo.
- Published
- 2000