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Pivagabine effects on neuroendocrine responses to experimentally-induced psychological stress in humans.

Abstract：

:Neuroendocrinology of chronic stress seems to be characterized by HPA axis hyperactivity and early childhood stressors have been hypothesized to predispose individuals to adult onset depression by means of dysregulation of the HPA axis. Pivagabine (PVG), a hydrophobic 4-aminobutyric acid derivative, has been used experimentally recently in the treatment of different disorders related to stress-maladaptation, because of its possible inhibitory action on corticotrophin releasing factor secretion and HPA axis function. In the present study, 20 healthy male subjects were each exposed twice to the same psychosocial stressor (stroop color-word interference task, public speaking and mental arithmetic in front of an audience) during a first session (day 1) and a second session (day 8). Plasma concentrations of norepinephrine (NE), epinephrine (EPI), adrenocorticotropic hormone (ACTH) and cortisol (CORT), heart rate (HR) and systolic blood pressure (SBP) were measured immediately before the beginning of the tests and at their end, 30 min later, on both experimental days. Utilizing a double blind schedule, the subjects received pivagabine (900 mg, twice a day)(PVG group: nine subjects) or placebo (PBO group: 11 subjects) during the 7 days between the two stress sessions. NE, EPI, ACTH, and CORT levels were significantly elevated after stress exposure on day 1 and day 8 in PBO group subjects. After PVG treatment, on day 8, ACTH, CORT, NE and EPI responses to stress were significantly blunted, together with HR and SBP, in PVG group subjects. These results add to the evidence concerning PVG capacity to inhibit the HPA axis in humans, in response to stressful stimuli, and suggest that the action of PVG may be mediated not only by GABAergic receptors, but also by the suppression of catecholamines response. PVG treatment could modulate HPA hyper-responsiveness to stress in subjects with negative affectivity and depressive traits.

journal_name

Behav Brain Res

journal_title

Behavioural brain research

authors

Gerra G,Zaimovic A,Giusti F,Baroni MC,Delsignore R,Raggi MA,Brambilla F

doi

10.1016/s0166-4328(01)00177-2

subject

Has Abstract

pub_date

2001-07-01 00:00:00

pages

93-101

issue

eissn

0166-4328

issn

1872-7549

pii

S0166-4328(01)00177-2

journal_volume

122

pub_type

临床试验,杂志文章,随机对照试验

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Pivagabine effects on neuroendocrine responses to experimentally-induced psychological stress in humans.