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The neurosteroid pregnenolone sulphate increases dopamine release and the dopaminergic response to morphine in the rat nucleus accumbens

Authors

  • Michel Barrot,

    1. Psychobiologie des Comportements Adaptatifs, INSERM U259, Université Victor Segalen Bordeaux 2, Rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France
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  • Monique Vallée,

    1. Psychobiologie des Comportements Adaptatifs, INSERM U259, Université Victor Segalen Bordeaux 2, Rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France
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  • Mireille A. Gingras,

    1. Psychobiologie des Comportements Adaptatifs, INSERM U259, Université Victor Segalen Bordeaux 2, Rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France
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  • Michel Le Moal,

    1. Psychobiologie des Comportements Adaptatifs, INSERM U259, Université Victor Segalen Bordeaux 2, Rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France
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  • Willy Mayo,

    1. Psychobiologie des Comportements Adaptatifs, INSERM U259, Université Victor Segalen Bordeaux 2, Rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France
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  • Pier Vincenzo Piazza

    1. Psychobiologie des Comportements Adaptatifs, INSERM U259, Université Victor Segalen Bordeaux 2, Rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France
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: Dr Pier Vincenzo Piazza, as above.
E-mail: pier-vincenzo.piazza@bordeaux.inserm.fr

Abstract

Neurosteroids are a subclass of steroids that can be synthesized in the central nervous system independently of peripheral sources. Clinical studies in humans have associated some of these hormones with a generic sensation of ‘well-being’ and with pathologies such as depression. In rodents, the neurosteroid pregnenolone sulphate (Preg-S) has been shown to present antidepressant-like effects. These observations suggest that neurosteroids could interact with reward-related processes, mood and motivation. However, the possible neural substrates of such an effect remain unclear. In this report, we studied the action of Preg-S on the activity of the mesencephalic dopaminergic projection to the nucleus accumbens which is considered one of the biological substrates of motivation and reward. Both the direct effect of Preg-S and the influence of this hormone on the dopaminergic response to the pharmacological reward provided by the opiate morphine, were studied by means of microdialysis. Pregnenolone sulphate dose-dependently increased dopamine release in the nucleus accumbens. Furthermore, this hormone doubled the dopaminergic response to morphine. These effects were observed for Preg-S doses of 100, 200, and 400 pmol injected intracerebroventricularly. The stimulant effect of Preg-S on dopamine could mediate some of the behavioural effects of neurosteroids and in particular the interaction of these hormones with mood and motivation.

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