Action of DHEA and DHEAS on the Central Nervous System: Effects on the Cell

N. Kalinkina

N. Kalinkina, M. Magich I.M. Sechenov Moscow Medical Academy, Russia

Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) produce a variety of effects in the central nervous system (CNS). It is believed that most effects are mediated via their non-genomic action on several neurotransmitter receptors. DHEA and DHEAS increase neuronal excitability, enhance neuronal plasticity, and possess neuroprotective properties. Previous studies demonstrated that treatment with DHEA is followed by a mood enhancing and antidepressant effect. Published data suggest that absolute and relative opiatergic insufficiency plays a considerable role in the development of alcohol, nicotine, and drug abuse. It was shown that the stress-limiting effects of DHEA are realized via the opiatergic, b-adrenergic, and adrenocorticotropic mechanisms at a level of the hypothalamic-pituitary-adrenocortical axis. The interaction of DHEA and DHEAS with the cerebral opiate system indicates that these substances are involved in the neuroendocrine mechanism of drug abuse. This work was performed to evaluate the role of DHEA and DHEAS in the neuronal mechanism of drug dependence. A direct correlation exists between emotional reactivity of humans and animals and the risk for development of drug abuse. Experiments were performed on Lewis and Wistar rats. The animals were subjected to an open-field test. After testing, they were divided into behaviorally active, passive, and intermediate groups. Pulse activity of lateral hypothalamic neurons was recorded before and after application of DHEA/DHEAS into the perineuronal space. In behaviorally active rats, patterns of neuronal activity primarily contained 5–20 and 100–200 ms interspike intervals. By contrast, neuronal activity in behaviorally passive animals was characterized by intervals with the duration of 30–50 and 100–200 ms. Microiontophoretic application of DHEAS into the perineuronal space of hypothalamic nerve cells increased the rate of neuronal pulse activity. However, DHEA applied with pressure decreased and regularized the firing rate of hypothalamic neurons. Our results suggest that DHEA, and DHEAS are involved in the neuronal mechanisms of drug abuse.

Abstract Year: 
2003
Abstract Region: 
East Asia
Abstract Country: 
Russian Federation