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Pharmacopsychiatry 2004; 37: 171-182
DOI: 10.1055/s-2004-832675
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Neurosteroids and σ1 Receptors, Biochemical and Behavioral Relevance

T. Maurice1
  • 1Laboratory of Cerebral Plasticity, CNRS FRE 2693, University of Montpellier II, Montpellier, France
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Publication History

Publication Date:
17 November 2004 (online)

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The σ1 receptor is a 223 amino acid protein sharing no homology with other mammalian protein. It is an intracellular protein present on the endoplasmic reticulum membrane, which can translocates to other organelles and plasma membranes after activation. Activation of the σ1 receptor results in modulation of calcium mobilization from inositol trisphosphate receptor-gated intracellular pools and, at the plasma membrane, in modulation of several neurotransmitter responses. Behaviorally, σ1 receptors are involved in learning and memory, response to stress and depression, psychostimulant-induced sensitization, vulnerability to addiction and pain perception. Numerous synthetic compounds bind to σ1 receptor, playing the role of activator/agonist or blocker/antagonist, and these include benzomorphans, neuroleptics, antidepressants, cocaine, peptides related to neuropeptide Y or calcitonin gene-related peptide. It is also the case of neuro(active)steroids, i. e., circulating neuroactive steroids and neurosteroids synthesized de novo by the brain, which appear as the most important endogenous modulators of σ1 receptor. Pregnenolone and dehydroepiandrosterone act as σ1 receptor agonists and progesterone is a potent antagonist. The present paper will review the molecular and biochemical features concerning the σ1 receptor and focus on the recent studies examining the impact of the neuro(active)steroid/σ1 receptor interaction on the antidepressant activity of σ1 receptor agonists in the context of neurodegenerative diseases.

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Dr. T. Maurice

CNRS FRE 2693

University of Montpellier II

cc 090

place Eugène Bataillon

34095 Montpellier cedex 5

France

Phone: +33/0 4 67 14 36 23

Fax: +33/0 4 67 14 42 51

Email: maurice@univ-montp2.fr

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