The role of dehydroepiandrosterone (DHEA) in drug-seeking behavior.

Conventional substance-abuse treatments have only had limited success especially for drugs such as cocaine, methamphetamine and nicotine. Newer data have begun to shed light on the complexity of the addictive process and new treatment approaches, including interference with brain neurosteroids, to attenuate drug-seeking behavior, are in advanced stages of development. Neurosteroids are synthesized in the brain and peripheral tissues, from cholesterol or steroidal precursors imported from peripheral sources. The most abundant neurosteroids in the human body are DHEA and its sulfate ester, DHEAS. These neurosteroids can act as modulators of neurotransmitter receptors, such as γ-aminobutyric-acid-type A (GABA(A)), NMDA, and sigma-1 receptors which may contribute to apparent enduring behavioral manifestations facilitated by substances of abuse. Neurosteroid concentrations respond to environmental and behavioral circumstances, such as stress and mood, both which are involved in the progression of substance use that advance substance addiction. This article reviews the current literature pertaining to neurosteroids and substances of abuse, focusing on DHEA, and discusses its role in drug-seeking behavior as suggested by preclinical observations.