Stress and drug abuse-related disorders: The promising therapeutic value of neurosteroids focus on pregnenolone-progesterone-allopregnanolone pathway

Tomaselli G(1), Vallée M(2).

Author information:
(1)INSERM U1215, Neurocentre Magendie, Group « Physiopathology and Therapeutic
Approaches of Stress-Related Disease », 146 Rue Léo Saignat, 33000 Bordeaux,
France; University of Bordeaux, 33000 Bordeaux, France.
(2)INSERM U1215, Neurocentre Magendie, Group « Physiopathology and Therapeutic
Approaches of Stress-Related Disease », 146 Rue Léo Saignat, 33000 Bordeaux,
France; University of Bordeaux, 33000 Bordeaux, France. Electronic address:
.

The pregnenolone-progesterone-allopregnanolone pathway is receiving increasing
attention in research on the role of neurosteroids in pathophysiology,
particularly in stress-related and drug use disorders. These disorders involve
an allostatic change that may result from deficiencies in allostasis or adaptive
responses, and may be downregulated by adjustments in neurotransmission by
neurosteroids. The following is an overview of findings that assess how
pregnenolone and/or allopregnanolone concentrations are altered in animal models
of stress and after consumption of alcohol or cannabis-type drugs, as well as in
patients with depression, anxiety, post-traumatic stress disorder or psychosis
and/or in those diagnosed with alcohol or cannabis use disorders. Preclinical
and clinical evidence shows that pregnenolone and allopregnanolone, operating
according to a different or common pharmacological profile involving GABAergic
and/or endocannabinoid system, may be relevant biomarkers of psychiatric
disorders for therapeutic purposes. Hence, ongoing clinical trials implicate
synthetic analogs of pregnenolone or allopregnanolone, and also modulators of
neurosteroidogenesis.

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Auteurs Bordeaux Neurocampus