Involvement of pregnane xenobiotic receptor in mating-induced allopregnanolone formation in the midbrain and hippocampus and brain-derived neurotrophic factor in the hippocampus among female rats.
BACKGROUND
Given that the pregnane neurosteroid, 5α-pregnan-3α-ol-20-one (3α,5α-THP), is increased following behavioral challenges (e.g., mating), and that there is behavioral-induced biosynthesis of 3α,5α-THP in midbrain and mesocorticolimbic structures, 3α,5α-THP likely has a role in homeostasis and motivated reproduction and reproduction-related behaviors (e.g., affect, affiliation). The role of pregnane xenobiotic receptor (PXR), involved in cholesterol metabolism, for these effects is of continued interest.


OBJECTIVE
We hypothesized that there would be differences in brain levels of 3α,5α-THP following varied behavioral experiences, an effect abrogated by knockdown of PXR in the midbrain.


METHODS
Proestrous rats were infused with PXR antisense oligonucleotides (AS-ODNs) or vehicle to the ventral tegmental area before different behavioral manipulations and assessments. Endpoints were expression levels of PXR in the midbrain, 3α,5α-THP, and ovarian steroids (estradiol, progesterone, dihydroprogesterone) in the midbrain, striatum, hippocampus, hypothalamus, prefrontal cortex, and plasma.


RESULTS
Across experiments, knocking down PXR reduced PXR expression and 3α,5α-THP levels in the midbrain and hippocampus. There were differences in terms of the behavioral manipulations, such that paced mating had the most robust effects to increase 3α,5α-THP levels and reduce open field exploration and social interaction. An additional question that was addressed is whether brain-derived neurotrophic factor (BDNF) is a downstream factor for regulating effects of behavioral-induced 3α,5α-THP biosynthesis. Rats infused with PXR AS-ODNs had lower levels of BDNF in the hippocampus.


CONCLUSIONS
Thus, PXR may be a regulator of mating-induced 3α,5α-THP formation and behavioral changes and neural plasticity, such as BDNF.
Department of Psychology, The University at Albany-SUNY, Life Sciences 01058, 1400 Washington Avenue, Albany, NY, 12222, USA, cheryl.a.frye@gmail.com.
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Frye
C J
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Koonce
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Walf
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003687:Dehydroepiandrosterone / Q000378:metabolism; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D008636:Mesencephalon / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D000077297:Pregnane X Receptor; D011280:Pregnanolone / Q000378:metabolism* / Q000494:pharmacology; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D011987:Receptors, Steroid / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012726:Sexual Behavior, Animal; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D016376:Oligonucleotides, Antisense; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D003687:Dehydroepiandrosterone; D011374:Progesterone; D011280:Pregnanolone