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

Autor(es)

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. ^{[2, 6]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: European Neuropsychopharmacology; v. 25, n. 1, p. 113-123, JAN 2015.
• Citações Web of Science: 12

Resumo

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)

• Processo FAPESP: 08/11408-2 - Avaliação comportamental, neuroquímica e imunohistoquímica do papel funcional de mecanismos serotoninérgicos da substância cinzenta periaquedutal dorsal e do núcleo dorsal da rafe em machos e fêmeas, em diferentes fases do ciclo estral.
• Beneficiário: Julia Maria dos Santos
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado