PMID- 19211896 OWN - NLM STAT- MEDLINE DCOM- 20090306 LR - 20211020 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 29 IP - 6 DP - 2009 Feb 11 TI - Viral vector-mediated overexpression of estrogen receptor-alpha in striatum enhances the estradiol-induced motor activity in female rats and estradiol-modulated GABA release. PG - 1897-903 LID - 10.1523/JNEUROSCI.4647-08.2009 [doi] AB - Classical estrogen receptor-signaling mechanisms involve estradiol binding to intracellular nuclear receptors [estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta)] to promote changes in protein expression. Estradiol can also exert effects within seconds to minutes, however, a timescale incongruent with genomic signaling. In the brain, estradiol rapidly potentiates stimulated dopamine release in the striatum of female rats and enhances spontaneous rotational behavior. Furthermore, estradiol rapidly attenuates the K(+)-evoked increase of GABA in dialysate. We hypothesize that these rapid effects of estradiol in the striatum are mediated by ERalpha located on the membrane of medium spiny GABAergic neurons. This experiment examined whether overexpression of ERalpha in the striatum would enhance the effect of estradiol on rotational behavior and the K(+)-evoked increase in GABA in dialysate. Ovariectomized female rats were tested for rotational behavior or underwent microdialysis experiments after unilateral intrastriatal injections of a recombinant adeno-associated virus (AAV) containing the human ERalpha cDNA (AAV.ERalpha) into the striatum; controls received either the same vector into areas outside the striatum or an AAV containing the human alkaline phosphatase gene into the striatum (AAV.ALP). Animals that received AAV.ERalpha in the striatum exhibited significantly greater estradiol-induced contralateral rotations compared with controls and exhibited behavioral sensitization of contralateral rotations induced by a low-dose of amphetamine. ERalpha overexpression also enhanced the inhibitory effect of estradiol on K(+)-evoked GABA release suggesting that disinhibition of dopamine release from terminals in the striatum resulted in the enhanced rotational behavior. FAU - Schultz, Kristin N AU - Schultz KN AD - Molecular and Behavioral Neuroscience Institute and Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA. FAU - von Esenwein, Silke A AU - von Esenwein SA FAU - Hu, Ming AU - Hu M FAU - Bennett, Amy L AU - Bennett AL FAU - Kennedy, Robert T AU - Kennedy RT FAU - Musatov, Sergei AU - Musatov S FAU - Toran-Allerand, C Dominique AU - Toran-Allerand CD FAU - Kaplitt, Michael G AU - Kaplitt MG FAU - Young, Larry J AU - Young LJ FAU - Becker, Jill B AU - Becker JB LA - eng GR - DA12677/DA/NIDA NIH HHS/United States GR - NS048141/NS/NINDS NIH HHS/United States GR - R01 NS048141-02/NS/NINDS NIH HHS/United States GR - R37 EB003320/EB/NIBIB NIH HHS/United States GR - R01 DA012677-06/DA/NIDA NIH HHS/United States GR - R01 DA012677-05/DA/NIDA NIH HHS/United States GR - R01 NS048141/NS/NINDS NIH HHS/United States GR - R01 DA012677/DA/NIDA NIH HHS/United States GR - R01 DA012677-08/DA/NIDA NIH HHS/United States GR - T32 DA007267/DA/NIDA NIH HHS/United States GR - R01 NS048141-03/NS/NINDS NIH HHS/United States GR - R01 DA012677-07/DA/NIDA NIH HHS/United States GR - R01 NS048141-04/NS/NINDS NIH HHS/United States GR - R01 NS048141-01/NS/NINDS NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Estrogen Receptor alpha) RN - 4TI98Z838E (Estradiol) RN - 56-12-2 (gamma-Aminobutyric Acid) SB - IM MH - Animals MH - Corpus Striatum/*metabolism/physiology/*virology MH - Dependovirus/genetics MH - Estradiol/genetics/*physiology MH - Estrogen Receptor alpha/administration & dosage/*biosynthesis/*genetics MH - Female MH - Gene Expression Regulation/*physiology MH - Genetic Vectors/administration & dosage/genetics MH - Humans MH - Motor Activity/genetics/*physiology MH - Rats MH - Rats, Sprague-Dawley MH - Sexual Behavior/physiology MH - gamma-Aminobutyric Acid/*metabolism PMC - PMC2655639 MID - NIHMS93860 EDAT- 2009/02/13 09:00 MHDA- 2009/03/07 09:00 PMCR- 2009/08/11 CRDT- 2009/02/13 09:00 PHST- 2009/02/13 09:00 [entrez] PHST- 2009/02/13 09:00 [pubmed] PHST- 2009/03/07 09:00 [medline] PHST- 2009/08/11 00:00 [pmc-release] AID - 29/6/1897 [pii] AID - 3452044 [pii] AID - 10.1523/JNEUROSCI.4647-08.2009 [doi] PST - ppublish SO - J Neurosci. 2009 Feb 11;29(6):1897-903. doi: 10.1523/JNEUROSCI.4647-08.2009.