Abstract:
RATIONALE:Greater incidence of anxiety and depressive disorders of women compared to men may be due in part to progesterone (P) and its neuroactive metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), acting in limbic regions, such as the amygdala. OBJECTIVE:If P's metabolism via 5alpha-reduction to 3alpha,5alpha-THP in the amygdala is critical for antianxiety and antidepressive behavior, then blocking 5alpha-reductase in the amygdala of female rats is likely to attenuate the antianxiety and antidepressive effects of high progestin levels from both endogenous and exogenous sources. METHODS:Naturally receptive female rats with high endogenous estrogen (E2) and P and ovariectomized (ovx) rats administered E2 (10 microg) and P (500 microg) subcutaneously were administered finasteride (10 microg/microl), a Type II 5alpha-reductase inhibitor, or vehicle to the amygdala. Anxiety behavior (open field, elevated plus maze, defensive freezing) and depressive behavior (Porsolt forced swim test) were assessed. RESULTS:There were similar effects of finasteride administration to the amygdala to attenuate antianxiety behavior in naturally receptive and ovx, hormone-primed rats. Finasteride administration significantly decreased central entries in the open field, decreased open arm time in the elevated plus maze, increased defensive freezing in response to footshock, and increased time spent immobile compared to vehicle. CONCLUSIONS:Thus, formation and subsequent actions of 3alpha,5alpha-THP in the amygdala may be important for antianxiety and antidepressive effects.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Walf AA,Sumida K,Frye CAdoi
10.1007/s00213-005-0100-xsubject
Has Abstractpub_date
2006-06-01 00:00:00pages
302-11issue
3eissn
0033-3158issn
1432-2072journal_volume
186pub_type
杂志文章abstract:INTRODUCTION:Genetic causes, or predisposition, are increasingly accepted to be part of the ethiopathogenesis of many neuropsychiatric diseases. While genes can be studied in any type of cells, their physiological function in human brain cells is difficult to evaluate, particularly in living subjects. METHODS:As a fir...
journal_title:Psychopharmacology
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pub_type: 临床试验,杂志文章
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pub_type: 临床试验,杂志文章
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doi:10.1007/s00213-011-2501-3
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pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Psychopharmacology
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更新日期:1993-01-01 00:00:00
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更新日期:2020-04-01 00:00:00