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

Rationale 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 an...

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Bibliographic Details
Published in:Psychopharmacology 2014-09, Vol.231 (17), p.3375-3390
Main Authors: Frye, C. A., Koonce, C. J., Walf, A. A.
Format: Article
Language:English
Subjects:
Animals
Biomedical and Life Sciences
Biomedicine
Brain
Brain-derived neurotrophic factor
Brain-Derived Neurotrophic Factor - metabolism
Dehydroepiandrosterone - metabolism
Dosage and administration
Drug interactions
Estrous Cycle - drug effects
Female
Health aspects
Hippocampus (Brain)
Hippocampus - metabolism
Identification and classification
Mesencephalon - metabolism
Neurology
Neurosciences
Oligonucleotides, Antisense - pharmacology
Original Investigation
Pharmacology/Toxicology
Pregnanolone - metabolism
Pregnanolone - pharmacology
Progesterone - metabolism
Psychiatry
Psychopharmacology
Rats
Rats, Long-Evans
Receptors, Steroid - drug effects
Receptors, Steroid - genetics
Receptors, Steroid - metabolism
Sexual Behavior, Animal
Steroids
Steroids (Drugs)
Ventral Tegmental Area - drug effects
Ventral Tegmental Area - metabolism
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Summary:Rationale 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. Objectives 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. Conclusion Thus, PXR may be a regulator of mating-induced 3α,5α-THP formation and behavioral changes and neural plasticity, such as BDNF.
ISSN:0033-3158
1432-2072
DOI:10.1007/s00213-014-3569-3