Serotonin increases the excitability of the hypothalamic paraventricular nucleus magnocellular neurons.
Recent evidence that 5-hydroxytryptamine (5-HT or serotonin) enhances the release and the gene expression of vasopressin and oxytocin in the hypothalamic paraventricular nucleus (PVN) suggests that 5-HT can excite the PVN magnocellular neurons. The objective of this study was to examine the underlying mechanisms for such excitatory action in the electrophysiologically identified hypothalamic PVN magnocellular neurons in rats using whole-cell patch-clamp. We found that 5-HT weakly depolarizes 33.3% of PVN magnocellular neurons in the presence of tetrodotoxin. A minuscule inward current was produced by 5-HT in 48% of the cells, which was attenuated when the 5-HT(4) antagonist GR113808 or the 5-HT(7) antagonist SB269970 was added. In addition, 5-HT reduced the frequency of miniature inhibitory postsynaptic currents in a dose-dependent manner. This inhibition was mimicked by the 5-HT(1B) agonist CP93129, and reversed in the presence of 5-HT(1B) antagonists cyanopindolol and SB224289. Besides, 5-HT induced a biphasic effect on the frequency of miniature excitatory postsynaptic currents, comprising a transient inhibition and a delayed concentration-dependent excitation (onset latency approximately 5 min). The facilitation was mimicked by the 5-HT(2A/2C) agonist DOI and abolished in the presence of the 5-HT(2C) antagonist RS102221. Our findings reveal that 5-HT directly increases the excitability of the PVN magnocellular neurons via multiple receptor subtypes and mechanisms. This may help understanding the regulation of 5-HT-induced hormone release and feeding behavior in the PVN.
Ho
Sara S N
SS
Department of Zoology, The University of Hong Kong, Pokfulam, Hong Kong, China.
Chow
Billy K C
BK
Yung
Wing-Ho
WH
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018756:GABA Antagonists; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D026941:Sodium Channel Blockers; D012701:Serotonin