Neurosteroids and the Nervous System by Steven R. King

Author:Steven R. King
Language: eng
Format: epub
Publisher: Springer New York, New York, NY

21 Substance Abuse

Considerable research focuses on the influence of neurosteroids in substance addiction and abuse [11], a topic beyond the scope of this review. Steroids play an instrumental role in reward, tolerance, and withdrawal behavior. These effects are partly traced to their modulation of the GABAA receptor. The reward effects of estradiol are linked to the activation of ERs in the nucleus accumbens [837].

Steroids also mitigate impairments in CNS function induced by drugs, as mentioned previously. For instance, DHEA and pregnenolone sulfate among other steroids prevent cognitive deficits caused by ethanol [419]. Pregnenolone and its sulfate conjugate as well as high-dose DHEA oppose ethanol-induced anxiolysis [342, 345]. Select steroids also inhibit seizures induced by cocaine [705] and nicotine in response to an auditory stimulus [236].

Drugs themselves can regulate steroid levels in the CNS. Central levels of neurosteroids such as allopregnanolone rise with the intake of alcohol and Δ9-tetrahydrocannabinol [11]. Chronic intermittent ethanol administration in rats reduces allopregnanolone along with its synthetic enzymes, 5α-reductase type I and 3αHSD [838]. This may be a cause of the increased anxiety and related behavioral changes observed in these animals.

Peripheral steroids such as those from the adrenal play a large role in drug effects and may contribute to or in some cases account for all the acute changes in CNS steroids. Roles for endogenous neurosteroids await future clarification.

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