PMID- 24744202
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  - Reduction of circulating and selective limbic brain levels of 
      (3alpha,5alpha)-3-hydroxy-pregnan-20-one (3alpha,5alpha-THP) following forced swim stress in 
      C57BL/6J mice.
PG  - 3281-92
LID - 10.1007/s00213-014-3552-z [doi]
AB  - RATIONALE: Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, and 
      GABAergic neuroactive steroids contribute to homeostatic regulation of this 
      circuitry. Acute forced swim stress (FSS) increases plasma, cortical, and 
      hypothalamic (3alpha,5alpha)-3-hydroxy-pregnan-20-one (3alpha,5alpha-THP) levels in rats. 
      However, there have not been systemic investigations of acute stress on changes 
      in plasma and brain levels of 3alpha,5alpha-THP in mouse models. OBJECTIVES: The present 
      experiments aimed to assess circulating and local brain levels of 3alpha,5alpha-THP 
      following acute FSS in C57BL/6J mice. METHODS: Mice were exposed to FSS (10 min), 
      and 50 min later, blood and brains were collected. Circulating pregnenolone and 
      3alpha,5alpha-THP levels were assessed in serum. Free-floating brain sections (40 mum, 
      four to five sections/region) were immunostained and analyzed in cortical and 
      limbic brain structures. RESULTS: FSS decreased circulating 3alpha,5alpha-THP 
      (-41.6 +/- 10.4 %) and reduced 3alpha,5alpha-THP immunolabeling in the paraventricular 
      nucleus of the hypothalamus (-15.2 +/- 5.7 %), lateral amygdala (LA, -31.1 +/- 13.4 
      %), and nucleus accumbens (NAcc) shell (-31.9 +/- 14.6). Within the LA, vesicular 
      glutamate transporter 1 (VGLUT1) and vesicular GABA transporter were localized in 
      3alpha,5alpha-THP-positively stained cells, while in the NAcc shell, only VGLUT1 was 
      localized in 3alpha,5alpha-THP-positively stained cells, suggesting that both 
      glutamatergic and GABAergic cells within the LA are 3alpha,5alpha-THP-positive, while in 
      the NAcc shell, 3alpha,5alpha-THP only localizes to glutamatergic cells. CONCLUSIONS: The 
      decrease in circulating and brain levels of 3alpha,5alpha-THP may be due to alterations 
      in the biosynthesis/metabolism or changes in the regulation of the HPA axis 
      following FSS. Changes in GABAergic neuroactive steroids in response to stress 
      likely mediate functional adaptations in neuronal activity. This may provide a 
      potential targeted therapeutic avenue to address maladaptive stress responsivity.
FAU - Maldonado-Devincci, Antoniette M
AU  - Maldonado-Devincci AM
AD  - Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, 
      3027 Thurston Bowles Building, CB 7178, Chapel Hill, NC, 27599, USA.
FAU - Beattie, Matthew C
AU  - Beattie MC
FAU - Morrow, Danielle H
AU  - Morrow DH
FAU - McKinley, Raechel E
AU  - McKinley RE
FAU - Cook, Jason B
AU  - Cook JB
FAU - O'Buckley, Todd K
AU  - O'Buckley TK
FAU - Morrow, A Leslie
AU  - Morrow AL
LA  - eng
GR  - P60 AA011605/AA/NIAAA NIH HHS/United States
GR  - T32 ES007126/ES/NIEHS NIH HHS/United States
GR  - U01 AA020935/AA/NIAAA NIH HHS/United States
GR  - UO1-AA020935/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140418
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Slc17a7 protein, mouse)
RN  - 0 (Vesicular Glutamate Transport Protein 1)
RN  - 0 (Vesicular Inhibitory Amino Acid Transport Proteins)
RN  - 0 (Viaat protein, mouse)
RN  - BXO86P3XXW (Pregnanolone)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Adrenal Glands/enzymology/metabolism
MH  - Animals
MH  - Brain Chemistry/drug effects
MH  - Corticosterone/blood
MH  - Limbic System/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pregnanolone/*metabolism
MH  - Stress, Psychological/*metabolism/psychology
MH  - Swimming/*psychology
MH  - Vesicular Glutamate Transport Protein 1/metabolism
MH  - Vesicular Inhibitory Amino Acid Transport Proteins/metabolism
PMC - PMC4335654
MID - NIHMS634298
COIS- Conflict of interest The authors declare no conflict of interest.
EDAT- 2014/04/20 06:00
MHDA- 2015/06/03 06:00
PMCR- 2015/09/01
CRDT- 2014/04/19 06:00
PHST- 2014/01/24 00:00 [received]
PHST- 2014/03/16 00:00 [accepted]
PHST- 2014/04/19 06:00 [entrez]
PHST- 2014/04/20 06:00 [pubmed]
PHST- 2015/06/03 06:00 [medline]
PHST- 2015/09/01 00:00 [pmc-release]
AID - 10.1007/s00213-014-3552-z [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2014 Sep;231(17):3281-92. doi: 
      10.1007/s00213-014-3552-z. Epub 2014 Apr 18.