PMID- 20562342 OWN - NLM STAT- MEDLINE DCOM- 20100830 LR - 20211020 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 107 IP - 27 DP - 2010 Jul 6 TI - Histaminergic responses by hypothalamic neurons that regulate lordosis and their modulation by estradiol. PG - 12311-6 LID - 10.1073/pnas.1006049107 [doi] AB - How do fluctuations in the level of generalized arousal of the brain affect the performance of specific motivated behaviors, such as sexual behaviors that depend on sexual arousal? A great deal of previous work has provided us with two important starting points in answering this question: (i) that histamine (HA) serves generalized CNS arousal and (ii) that heightened electrical activity of neurons in the ventromedial nucleus of the hypothalamus (VMN) is necessary and sufficient for facilitating the primary female sex behavior in laboratory animals, lordosis behavior. Here we used patch clamp recording technology to analyze HA effects on VMN neuronal activity. The results show that HA acting through H1 receptors (H1R) depolarizes these neurons. Further, acute administration of estradiol, an estrogen necessary for lordosis behavior to occur, heightens this effect. Hyperpolarization, which tends to decrease excitability and enhance inhibition, was not affected by acute estradiol or mediated by H1R but was mediated by other HA receptor subtypes, H2 and H3. Sampling of mRNA from individual VMN neurons showed colocalization of expression of H1 receptor mRNA with estrogen receptor (ER)-alpha mRNA but also revealed ER colocalization with the other HA receptor subtypes and colocalization of different subtypes with each other. The latter finding provides the molecular basis for complex "push-pull" regulation of VMN neuronal excitability by HA. Thus, in the simplest causal route, HA, acting on VMN neurons through H1R provides a mechanism by which elevated states of generalized CNS arousal can foster a specific estrogen-dependent, aroused behavior, sexual behavior. FAU - Dupre, Christophe AU - Dupre C AD - Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY 10065, USA. FAU - Lovett-Barron, Matthew AU - Lovett-Barron M FAU - Pfaff, Donald W AU - Pfaff DW FAU - Kow, Lee-Ming AU - Kow LM LA - eng GR - T32 HD007430/HD/NICHD NIH HHS/United States GR - HD05751/HD/NICHD NIH HHS/United States GR - R37 HD005751/HD/NICHD NIH HHS/United States GR - MH38273/MH/NIMH NIH HHS/United States GR - R01 HD005751/HD/NICHD NIH HHS/United States GR - R01 MH038273/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20100618 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Histamine Agonists) RN - 0 (Histamine Antagonists) RN - 0 (Receptors, Estrogen) RN - 0 (Receptors, Histamine H1) RN - 0 (Receptors, Histamine H2) RN - 0 (Receptors, Histamine H3) RN - 4TI98Z838E (Estradiol) RN - 820484N8I3 (Histamine) SB - IM MH - Animals MH - Estradiol/*pharmacology MH - Female MH - Gene Expression MH - Histamine/*pharmacology MH - Histamine Agonists/pharmacology MH - Histamine Antagonists/pharmacology MH - Membrane Potentials/drug effects MH - Neurons/*drug effects/metabolism/physiology MH - Patch-Clamp Techniques MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Estrogen/genetics/physiology MH - Receptors, Histamine H1/genetics/physiology MH - Receptors, Histamine H2/genetics/physiology MH - Receptors, Histamine H3/genetics/physiology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Sexual Behavior, Animal/physiology MH - Ventromedial Hypothalamic Nucleus/cytology PMC - PMC2901472 COIS- The authors declare no conflict of interest. EDAT- 2010/06/22 06:00 MHDA- 2010/08/31 06:00 PMCR- 2011/01/06 CRDT- 2010/06/22 06:00 PHST- 2010/06/22 06:00 [entrez] PHST- 2010/06/22 06:00 [pubmed] PHST- 2010/08/31 06:00 [medline] PHST- 2011/01/06 00:00 [pmc-release] AID - 1006049107 [pii] AID - 201006049 [pii] AID - 10.1073/pnas.1006049107 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2010 Jul 6;107(27):12311-6. doi: 10.1073/pnas.1006049107. Epub 2010 Jun 18.