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The Journal of Neuroscience, February 1, 2003, 23(3):788

Oxytocin Regulates Neurosteroid Modulation of GABA_A Receptors in Supraoptic Nucleus around Parturition

Jan-Jurjen Koksma¹, Ronald E. van Kesteren², Thomas W. Rosahl³, Ruud Zwart⁴, August B. Smit², Hartmut Lüddens⁵, and Arjen B. Brussaard¹

Departments of ¹ Experimental Neurophysiology and ² Molecular and Cellular Neurobiology, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands, ³ Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Harlow, Essex, CM20 2QR, United Kingdom, ⁴ Research Institute of Toxicology, Utrecht University, NL-3508 TD Utrecht, The Netherlands, and ⁵ Department of Psychiatry, Clinical Research Group, University of Mainz, Mainz, 55131, Germany

In this study, we investigate how neurosteroid sensitivity of GABA_A receptors (GABA_ARs) is regulated. We examined this issue in neurons of the supraoptic nucleus (SON) of the rat and found that, during parturition, the GABA_ARs become insensitive to the neurosteroid allopregnanolone attributable to a shift in the balance between the activities of endogenous Ser/Thr phosphatase and PKC. In particular, a constitutive endogenous tone of oxytocin within the SON after parturition suppressed neurosteroid sensitivity of GABA_ARs via activation of PKC. Vice versa before parturition, during late pregnancy, application of exogenous oxytocin brings the GABA_ARs from a neurosteroid-sensitive mode toward a condition in which the receptors are not sensitive. This indicates that there may be an inverse causal relationship between the extent to which the GABA_AR or one of its interacting proteins is phosphorylated and the neurosteroid sensitivity of the GABA_AR. Neurosteroid sensitivity was not affected by changes in subunit composition of GABA_ARs known to occur concurrently in these cells.

Key words: neurosteroid; GABAA receptor; supraoptic nucleus; PKC; phosphatase; oxytocin

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Copyright © 2003 Society for Neuroscience  0270-6474/03/233788-10$05.00/0

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