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

Neurosteroids are a subclass of steroids that can be synthesized in the cen tral nervous system independently of peripheral sources. Clinical studies i n humans have associated some of these hormones with a generic sensation of 'well-being' and with pathologies such as depression. In rodents, the neur osteroid pregnenolone sulphate (Preg-S) has been shown to present antidepre ssant-like effects. These observations suggest that neurosteroids could int eract with reward-related processes, mood and motivation. However, the poss ible neural substrates of such an effect remain unclear. In this report, we studied the actin of Preg-S on the activity of the mesencephalic dopaminer gic projection to the nucleus accumbens which is considered one of the biol ogical substrates of motivation and reward. Both the direct effect of Preg- S and the influence of this hormone on the dopaminergic response to the pha rmacological 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 do paminergic response to morphine. These effects were observed for Preg-S dos es of 100, 200 and 400 pmol injected intracerebroventricularly. The stimula nt effect of Preg-S on dopamine could mediate some of the behavioral effect s of neurosteroids an din particular the interaction of these hormones with mood and motivation.