title: GABAergic inhibition is weakened or converted into excitation in the oxytocin and vasopressin neurons of the lactating rat.
abstract: BACKGROUND
  Increased secretion of oxytocin and arginine vasopressin (AVP) from hypothalamic magnocellular neurosecretory cells (MNCs) is a key physiological response to lactation. In the current study, we sought to test the hypothesis that the GABAA receptor-mediated inhibition of MNCs is altered in lactating rats.
  
  
  RESULTS
  Gramicidin-perforated recordings in the rat supraoptic nucleus (SON) slices revealed that the reversal potential of GABAA receptor-mediated response (EGABA) of MNCs was significantly depolarized in the lactating rats as compared to virgin animals. The depolarizing EGABA shift was much larger in rats in third, than first, lactation such that GABA exerted an excitatory, instead of inhibitory, effect in most of the MNCs of these multiparous rats. Immunohistochemical analyses confirmed that GABAergic excitation was found in both AVP and oxytocin neurons within the MNC population. Pharmacological experiments indicated that the up-regulation of the Cl(-) importer Na(+)-K(+)-2Cl(-) cotransporter isotype 1 and the down-regulation of the Cl(-) extruder K(+)-Cl(-) cotransporter isotype 2 were responsible for the depolarizing shift of EGABA and the resultant emergence of GABAergic excitation in the MNCs of the multiparous rats.
  
  
  CONCLUSIONS
  We conclude that, in primiparous rats, the GABAergic inhibition of MNCs is weakened during the period of lactation while, in multiparous females, GABA becomes excitatory in a majority of the cells. This reproductive experience-dependent alteration of GABAergic transmission may help to increase the secretion of oxytocin and AVP during the period of lactation.
authors.affiliation: Department of Physiology, Korea University College of Medicine, 126-1 Anam-dong 5-ga, Seoul, 136-705, Republic of Korea. cslewis00@korea.ac.kr.
authors.forename: Seung Won
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Physiology, Korea University College of Medicine, 126-1 Anam-dong 5-ga, Seoul, 136-705, Republic of Korea. floweransi@korea.ac.kr.
authors.forename: Young-Beom
authors.initials: YB
authors.lastname: Kim
authors.affiliation: Department of Physiology, Biomedical Science Institute & Medical Research Center, School of Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea. 96rachel@hanmail.net.
authors.forename: Jeong Sook
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Physiology, Korea University College of Medicine, 126-1 Anam-dong 5-ga, Seoul, 136-705, Republic of Korea. kimwoongbin@korea.ac.kr.
authors.forename: Woong Bin
authors.initials: WB
authors.lastname: Kim
authors.affiliation: Department of Physiology, Korea University College of Medicine, 126-1 Anam-dong 5-ga, Seoul, 136-705, Republic of Korea. bluehawrk@korea.ac.kr.
authors.forename: Yoon Sik
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Physiology, Korea University College of Medicine, 126-1 Anam-dong 5-ga, Seoul, 136-705, Republic of Korea. heehan@korea.ac.kr.|Neuroscience Research Institute, Korea University College of Medicine, Seoul, 136-705, Republic of Korea. heehan@korea.ac.kr.
authors.forename: Hee Chul
authors.initials: HC
authors.lastname: Han
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California-Los Angeles, Los Angeles, CA, 90024, USA. CColwell@mednet.ucla.edu.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Colwell
authors.affiliation: Department of Physiology, Biomedical Science Institute & Medical Research Center, School of Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea. ywcho@khu.ac.kr.
authors.forename: Young-Wuk
authors.initials: YW
authors.lastname: Cho
authors.affiliation: Department of Physiology, Korea University College of Medicine, 126-1 Anam-dong 5-ga, Seoul, 136-705, Republic of Korea. yikim@korea.ac.kr.|Neuroscience Research Institute, Korea University College of Medicine, Seoul, 136-705, Republic of Korea. yikim@korea.ac.kr.
authors.forename: Yang
authors.initials: Y
authors.lastname: In Kim
mesh_terms: D000200:Action Potentials; D000818:Animals; D015536:Down-Regulation; D005260:Female; D059330:GABAergic Neurons / Q000378:metabolism*; D007150:Immunohistochemistry; D007774:Lactation / Q000378:metabolism*; D008892:Milk; D009433:Neural Inhibition; D010121:Oxytocin / Q000378:metabolism*; D010298:Parity; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2 / Q000378:metabolism; D027981:Symporters / Q000378:metabolism; D015854:Up-Regulation; D014667:Vasopressins / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000096922:K Cl- Cotransporters
chemical_list: D010121:Oxytocin; D011963:Receptors, GABA-A; D064506:Solute Carrier Family 12, Member 2; D027981:Symporters; D014667:Vasopressins; D005680:gamma-Aminobutyric Acid; D000096922:K Cl- Cotransporters; C578879:Slc12a2 protein, rat