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Sex differences and effects of prenatal exposure to excess testosterone on ventral tegmental area dopamine neurons in adult sheep

dc.contributor.authorBrown, Erinna C. Z.en_US
dc.contributor.authorSteadman, Casey J.en_US
dc.contributor.authorLee, Theresa M.en_US
dc.contributor.authorPadmanabhan, Vasanthaen_US
dc.contributor.authorLehman, Michael N.en_US
dc.contributor.authorCoolen, Lique M.en_US
dc.date.accessioned2015-05-04T20:36:11Z
dc.date.available2016-07-05T17:27:59Zen
dc.date.issued2015-05en_US
dc.identifier.citationBrown, Erinna C. Z.; Steadman, Casey J.; Lee, Theresa M.; Padmanabhan, Vasantha; Lehman, Michael N.; Coolen, Lique M. (2015). "Sex differences and effects of prenatal exposure to excess testosterone on ventral tegmental area dopamine neurons in adult sheep." European Journal of Neuroscience 41(9): 1157-1166.en_US
dc.identifier.issn0953-816Xen_US
dc.identifier.issn1460-9568en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/111123
dc.description.abstractPrenatal testosterone (T) excess in sheep results in a wide array of reproductive neuroendocrine deficits and alterations in motivated behavior. The ventral tegmental area (VTA) plays a critical role in reward and motivated behaviors and is hypothesised to be targeted by prenatal T. Here we report a sex difference in the number VTA dopamine cells in the adult sheep, with higher numbers of tyrosine hydroxylase (TH)‐immunoreactive (‐ir) cells in males than females. Moreover, prenatal exposure to excess T during either gestational days 30–90 or 60–90 resulted in increased numbers of VTA TH‐ir cells in adult ewes compared to control females. Stereological analysis confirmed significantly greater numbers of neurons in the VTA of males and prenatal T‐treated ewes, which was primarily accounted for by greater numbers of TH‐ir cells. In addition, immunoreactivity for TH in the cells was denser in males and prenatal T‐treated females, suggesting that sex differences and prenatal exposure to excess T affects both numbers of cells expressing TH and the protein levels within dopamine cells. Sex differences were also noted in numbers of TH‐ir cells in the substantia nigra, with more cells in males than females. However, prenatal exposure to excess T did not affect numbers of TH‐ir cells in the substantia nigra, suggesting that this sex difference is organised independently of prenatal actions of T. Together, these results demonstrate sex differences in the sheep VTA dopamine system which are mimicked by prenatal treatment with excess T.We report a sex difference in ventral tegmental area (VTA) dopamine cells in the adult sheep with higher numbers of tyrosine hydroxylase (TH)‐immunoreactive cells in males than females. Moreover, prenatal exposure to excess T during gestational days 30–90 or 60–90 caused increased numbers of VTA TH‐immunoreactive cells in adult ewes compared to control females. Sex differences were also demonstrated in the substantia nigra, but prenatal T had no effect on TH in this area. Results indicate that sex differences and prenatal exposure to excess T affects both numbers of cells expressing TH and the protein levels in the VTA.en_US
dc.publisherWiley Periodicals, Inc.en_US
dc.subject.othermesolimbicen_US
dc.subject.othermidbrainen_US
dc.subject.otherrewarden_US
dc.subject.othersex dimorphismen_US
dc.subject.othersteroiden_US
dc.titleSex differences and effects of prenatal exposure to excess testosterone on ventral tegmental area dopamine neurons in adult sheepen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelNeurosciencesen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/111123/1/ejn12871.pdf
dc.identifier.doi10.1111/ejn.12871en_US
dc.identifier.sourceEuropean Journal of Neuroscienceen_US
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