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Structure-activity relationship studies on neuroactive steroids in memory, alcohol and stress-related functions: a crucial benefit from endogenous level analysis

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Abstract

Rationale

New research findings in the field of neuroactive steroids strongly suggest that to understand their role in physiopathology, it is essential to accurately measure their tissue levels. Through his broad chemical expertise and extensive knowledge of steroids, Dr. Robert H. Purdy pioneered structure-activity relationship studies on these compounds and developed innovative detection assays that are essential to assess their function in biological tissues.

Objective

The goal of the present paper is to point out the specific contributions of Dr. Purdy and his collaborators to the current knowledge on the role of neuroactive steroids in the modulation of memory and alcohol- and stress-related effects with particular emphasis on the detection assays he developed to assess their endogenous levels. Reviewed here are the major results as well as the original and valuable methodological strategies issued by the long-term collaboration between Dr Purdy and many scientists worldwide on the investigation of the structure-activity relationship of neuroactive steroids.

Results

Altogether, the data presented herein put forward the original notion that knowledge of the chemical structure of steroids is essential for their detection and the understanding of their role in physiological and pathological conditions, including the stress response.

Conclusions

The current challenge is to identify and quantify using appropriate methods neuroactive steroids in the context of both animal and clinical studies in order to reveal how their levels change under physiological and disease states. Dr. Purdy passed away in September 2012, but scientists all over the world will always be grateful for his pioneering work on steroid chemistry and for his great enthusiasm in research.

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Abbreviations

ent-PREGS:

(-) PREGS enantiomer

3α,5α-THDOC:

3α,5α-Tetrahydrodeoxycorticosterone

3α,5α-THPROG allopregnanolone:

3α,5α-Tetrahydroprogesterone

3α,β THPROG pregnanolone:

3α,5β-Tetrahydroprogesterone

3β,5α-THPROG epiallopregnanolone:

3β,5α-Tetrahydroprogesterone

5α-DHPROG:

5α-Dihydroxyprogesterone

DHEA:

Dehydroepiandrosterone

GC:

Gas chromatography

LC:

Liquid chromatography

MS:

Mass spectrometry

NMDA:

N-Methyl-d-aspartate

PREG:

Pregnenolone

PROG:

Progesterone

RIA:

Radioimmunoassay

UCS:

Unpredictable chronic stress

GABA:

γ-Aminobutyric acid A

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Acknowledgments

We are grateful to Agnès Grel, Sergio Vitiello and Cédric Dupuy for the technical help. Supported by INSERM, the University Victor Segalen-Bordeaux2, Structure Fédérative de Recherche Neurosciences (SFRn) de l’Université de Bordeaux and Region Aquitaine funds. All animal procedures were performed in accordance with the National Institutes of Health Guide For the Care and Use of Laboratory Animals (National Research Council, 1985) and the French and European Communities Council Directive (86/609/EEC) and approved by the Institutional Animal Care and Use Committee of The Scripps Research Institute or the Aquitaine-Poitou Charentes ethical committee.

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  1. INSERM U862, Neurocentre Magendie, Pathophysiology of Addiction, Bordeaux, 33077, France

    Monique Vallée

  2. Université de Bordeaux, Bordeaux, 33077, France

    Monique Vallée

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Correspondence to Monique Vallée.

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Vallée, M. Structure-activity relationship studies on neuroactive steroids in memory, alcohol and stress-related functions: a crucial benefit from endogenous level analysis. Psychopharmacology 231, 3243–3255 (2014). https://doi.org/10.1007/s00213-014-3593-3

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  • DOI: https://doi.org/10.1007/s00213-014-3593-3

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