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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Elevation of brain allopregnanolone rather than 5-HT release by short term, low dose fluoxetine treatment prevents the estrous cycle-linked increase in stress sensitivity in female rats

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Devall, Adam J. [1] ; Santos, Julia M. [2, 1, 3] ; Fry, Jonathan P. [4] ; Honour, John W. [5] ; Brandao, Marcus L. [2, 3] ; Lovick, Thelma A. [6, 2]
Total Authors: 6
[1] Univ Birmingham, Sch Clin & Expt Med, Birmingham B15 2TT, W Midlands - England
[2] Inst Neurociencias & Comportamento INeC, BR-14040901 Ribeirao Preto, SP - Brazil
[3] Univ Sao Paulo, Lab Psicobiol, Fac Filosofia Ciencias & Letras Ribeirao Preto, BR-14040901 Ribeirao Preto, SP - Brazil
[4] UCL, Dept Neurosci Physiol & Pharmacol, London W1E 6BT - England
[5] Univ Coll London Hosp, London NW1 2BU - England
[6] Univ Bristol, Sch Physiol & Pharmacol, Bristol BS8 1TD, Avon - England
Total Affiliations: 6
Document type: Journal article
Source: European Neuropsychopharmacology; v. 25, n. 1, p. 113-123, JAN 2015.
Web of Science Citations: 12

Withdrawal from long-term dosing with exogenous progesterone precipitates increased anxiety-linked changes in behavior in animal models due to the abrupt decrease in brain concentration of allopregnanolone (ALLO), a neuroactive metabolite of progesterone. We show that a withdrawal-like effect also occurs during the late diestrus phase (LD) of the natural ovarian cycle in rats, when plasma progesterone and ALLO are declining but estrogen secretion maintains a stable low level. This effect at LD was prevented by short-term treatment with low dose fluoxetine. During LD, but not at other stages of the estrous cycle, exposure to anxiogenic stress induced by whole body vibration at 4 Hz for 5 min evoked a significant decrease in tail flick latency (stress-induced hyperalgesia) and a decrease in the number of Fos-positive neurons present in the periaqueductal gray (PAG). The threshold to evoke fear-like behaviors in response to electrical stimulation of the dorsal PAG was lower in the LD phase, indicating an increase in the intrinsic excitability of the PAG circuitry. All these effects were blocked by short-term administration of fluoxetine (2 x 1.75 mg kg(-1) i.p.) during LD. This dosage increased the whole brain concentration of ALLO, as determined using gas chromatography-mass spectrometry, but was without effect on the extracellular concentration of 5-HT in the dorsal PAG, as measured by microdialysis. We suggest that fluoxetine-induced rise in brain ALLO concentration during LD offsets the sharp physiological decline, thus removing the trigger for the development of anxiogenic withdrawal effects. Crown Copyright (C) 2014 Published by Elsevier B.V. All rights reserved. (AU)

FAPESP's process: 08/11408-2 - Functional role of serotonergic mechanisms of the dorsal periaqueductal grey matter and dorsal raphe nucleus in males and females at different stages of the oestrous cycle: a behavioural, biochemistry and immunohistochemical study.
Grantee:Julia Maria dos Santos
Support Opportunities: Scholarships in Brazil - Post-Doctorate