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This Article Full Text Full Text (PDF) All Versions of this Article: 102/3/1459    most recent 91160.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Fukushima, T. Articles by Hori, Y. PubMed PubMed Citation Articles by Fukushima, T. Articles by Hori, Y.

Facilitatory Actions of Serotonin Type 3 Receptors on GABAergic Inhibitory Synaptic Transmission in the Spinal Superficial Dorsal Horn

¹Department of Physiology and Biological Information, Dokkyo Medical University School of Medicine, Tochigi; and ²Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi, Japan

Submitted 21 October 2008; accepted in final form 4 April 2009

Abstract

Analgesic effects of serotonin (5-hydroxytryptamine [5-HT]) type 3 (5-HT₃) receptors may involve the release of -aminobutyric acid (GABA) in the spinal dorsal horn. However, the precise synaptic mechanisms for 5-HT₃ receptor-mediated spinal analgesia are not clear. In this study, we investigated whether GABAergic neurons in the superficial dorsal horn (SDH) express functional 5-HT₃ receptors and how these 5-HT₃ receptors affect GABAergic inhibitory synaptic transmission in the SDH, by using slice preparations from adult glutamate decarboxylase 67–green fluorescent protein (GAD67-GFP) knock-in mice. Tight-seal whole cell recordings from GFP-positive and -negative neurons showed that 5-HT₃ receptor-specific agonist 2-methyl-serotonin (2-Me-5-HT) induced inward currents in a substantial population of both GFP-positive and -negative neurons. Additionally, we confirmed expression of 5-HT₃ receptors in both types of neurons by single-cell reverse transcription–polymerase chain reaction (RT-PCR) analysis. Further, GABA_A receptor-mediated inhibitory postsynaptic currents (IPSCs)—both those evoked by electrical stimulation and those occurring spontaneously in tetrodotoxin (i.e., miniature IPSCs [mIPSCs])—were recorded from GFP-negative neurons. 2-Me-5-HT increased the amplitude of the evoked IPSCs and the frequency of mIPSCs. The amplitude of mIPSCs was not affected by 2-Me-5-HT, suggesting that 5-HT augments GABAergic synaptic transmission via presynaptic mechanisms. The present observations indicate that 5-HT₃ receptors are expressed on both somadendritic regions and presynaptic terminals of GABAergic neurons and regulate GABA_A receptor-mediated inhibitory synaptic transmission in the SDH. Taken together, these results provide clues for the underlying mechanisms of the antinociceptive actions of 5-HT₃ receptors in the spinal dorsal horn.