PMID- 24781516
OWN - NLM
STAT- MEDLINE
DCOM- 20150602
LR  - 20211021
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 231
IP  - 17
DP  - 2014 Sep
TI  - 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.
PG  - 3375-90
LID - 10.1007/s00213-014-3569-3 [doi]
AB  - RATIONALE: Given that the pregnane neurosteroid, 5alpha-pregnan-3alpha-ol-20-one 
      (3alpha,5alpha-THP), is increased following behavioral challenges (e.g., mating), and 
      that there is behavioral-induced biosynthesis of 3alpha,5alpha-THP in midbrain and 
      mesocorticolimbic structures, 3alpha,5alpha-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 3alpha,5alpha-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, 3alpha,5alpha-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 3alpha,5alpha-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 3alpha,5alpha-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 3alpha,5alpha-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 3alpha,5alpha-THP 
      formation and behavioral changes and neural plasticity, such as BDNF.
FAU - Frye, C A
AU  - Frye CA
AD  - Department of Psychology, The University at Albany-SUNY, Life Sciences 01058, 
      1400 Washington Avenue, Albany, NY, 12222, USA, cheryl.a.frye@gmail.com.
FAU - Koonce, C J
AU  - Koonce CJ
FAU - Walf, A A
AU  - Walf AA
LA  - eng
GR  - R01 MH067698/MH/NIMH NIH HHS/United States
GR  - R56 MH067698/MH/NIMH NIH HHS/United States
GR  - MH0676980/MH/NIMH NIH HHS/United States
GR  - RMH067698B/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140501
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Pregnane X Receptor)
RN  - 0 (Receptors, Steroid)
RN  - 459AG36T1B (Dehydroepiandrosterone)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - BXO86P3XXW (Pregnanolone)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Dehydroepiandrosterone/metabolism
MH  - Estrous Cycle/drug effects
MH  - Female
MH  - Hippocampus/*metabolism
MH  - Mesencephalon/*metabolism
MH  - Oligonucleotides, Antisense/pharmacology
MH  - Pregnane X Receptor
MH  - Pregnanolone/*metabolism/pharmacology
MH  - Progesterone/metabolism
MH  - Rats
MH  - Rats, Long-Evans
MH  - Receptors, Steroid/drug effects/genetics/*metabolism
MH  - *Sexual Behavior, Animal
MH  - Ventral Tegmental Area/drug effects/metabolism
PMC - PMC4135012
MID - NIHMS591049
COIS- Conflict of Interest: All authors report that they have no conflicts of interest 
      (financial or otherwise) that would bias them to the outcome of these 
      experiments.
EDAT- 2014/05/02 06:00
MHDA- 2015/06/03 06:00
PMCR- 2015/09/01
CRDT- 2014/05/01 06:00
PHST- 2013/12/30 00:00 [received]
PHST- 2014/03/31 00:00 [accepted]
PHST- 2014/05/01 06:00 [entrez]
PHST- 2014/05/02 06:00 [pubmed]
PHST- 2015/06/03 06:00 [medline]
PHST- 2015/09/01 00:00 [pmc-release]
AID - 10.1007/s00213-014-3569-3 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2014 Sep;231(17):3375-90. doi: 
      10.1007/s00213-014-3569-3. Epub 2014 May 1.