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 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.
Barrot
M
M
Psychobiologie des Comportements Adaptatifs, INSERM U259, Université Victor Segalen Bordeaux 2, France.
Vallée
M
M
Gingras
M A
MA
Le Moal
M
M
Mayo
W
W
Piazza
P V
PV
D000339:Affect / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D017551:Microdialysis; D009020:Morphine / Q000494:pharmacology*; D009042:Motivation; D009294:Narcotics / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D011284:Pregnenolone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward
D009294:Narcotics; C018370:pregnenolone sulfate; D011284:Pregnenolone; D009020:Morphine; D004298:Dopamine