Rôle des psychostimulants sur l'axe du stress
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The health of mammals depends on their ability to maintain and/or restore homeostasis when faced with threats to the consistency of the "milieu intérieur". The organization of the response to these homeostatic threats ("stressors") consists of a stimulus input, a central processing system, and a response output. One of main system responsible for restoring homeostasis is the hypothalamic-pituitary-adrenal (HPA) axis which, in response to stressors, orchestrates the production of corticotropin-releasing factor (CRF) and vasopressin (VP) from the paraventricular nucleus (PVN) of the hypothalamus, of ACTH from the pituitary and of corticosteroids from the adrenals.
Exposure to drugs such as alcohol represents a homeostatic challenge and as expected, it stimulates the HPA axis in laboratory animals and human beings. This presentation discusses some of the mechanisms involved in this response. We first illustrate the activation of the HPA axis by acute alcohol injection, exemplified by increases in plasma ACTH levels (a response that depends on the presence of endogenous CRF and VP) and the upregulation of the PVN neuronal response (which involves CRF, CRF receptors and VP cell bodies). We then describe our recent studies investigating the long-term effect, of alcohol. This paradigm consists in exposing rats to three consecutive daily injections of alcohol or exposure to another stressor, then investigating their HPA axis response to, an acute alcohol injection administered 3-12 days later. Overall, we demonstrate that while an initial alcohol exposure significantly stimulates HPA axis activity in terms of PVN (CRF) neuronal activity and ACTH release, subsequent endocrine responses to, additional drug treatments are significantly blunted. We propose that if this phenomenon of selective tolerance takes place in humans, it may play a role in drug-seeking behaviors because some individuals may try to restore their initial HPA axis response by consuming increasing doses of alcohol.
Dernière mise à jour : vendredi 8 octobre 1999 19:18:14
Dr Jean-Michel Thurin