Dehydroepiandrosterone Attenuates Cocaine‐Seeking Behaviour Independently of Corticosterone Fluctuations

Abstract

The neurosteroid dehydroepiandrosterone (DHEA) is involved in the pathophysiology of several psychiatric disorders, including cocaine addiction. We have previously shown that DHEA attenuates cocaine-seeking behaviour, and also that DHEA decreases corticosterone (CORT) levels in plasma and the prefrontal cortex. Previous studies have found that rats demonstrate cocaine-seeking behaviour only when the level of CORT reaches a minimum threshold. In the present study, we investigated whether the attenuating effect of DHEA on cocaine seeking is a result of it reducing CORT levels rather than a result of any unique neurosteroid properties. Rats received either daily DHEA injections (2 mg/kg, i.p.) alone, daily DHEA (2 mg/kg, i.p.) with CORT infusion (to maintain stable basal levels of CORT; 15 mg/kg, s.c.) or vehicle (i.p.) as control, throughout self-administration training and extinction sessions. We found that both DHEA-treated and DHEA + CORT-treated groups showed a significantly lower number of active lever presses compared to controls throughout training and extinction sessions, as well as at cocaine-primed reinstatement. DHEA-treated rats showed lower CORT levels throughout the experimental phases compared to DHEA + CORT-treated and control rats. Additionally, we show that DHEA administered to cocaine-trained rats throughout extinction sessions, or immediately before reinstatement, attenuated cocaine seeking. These findings indicate that DHEA attenuates cocaine-seeking behaviour independently of fluctuations in CORT levels.

The 5α-reductase inhibitor finasteride reduces opioid self-administration in animal models of opioid use disorder

“…Furthermore, previous reports showed that repeated DHEAS treatment prevents the development of opioid tolerance without showing an effect on self-administration (70). Additionally, chronic treatment with DHEA has also been shown to reduce cocaine self-administration and reinstatement in rats (71).…”

The 5α-reductase inhibitor finasteride reduces opioid self-administration

“…Furthermore, previous reports describe a link between DHEAS and the development of opioid tolerance without showing an effect on self-administration 72 . Additionally, chronic treatment with DHEA has also been shown to reduce cocaine self-administration and reinstatement in rats 73 .…”

The Effect of Dehydroepiandrosterone Administration during Rehabilitation on White Matter Integrity Among Individuals With Polysubstance Use Disorder

“…In rodents, DHEA administration attenuated cocaine self-administration and decreased cocaine-seeking behaviors. [3][4][5] In humans, high levels of circulatory DHEA sulfate (DHEA-S) were associated with lower relapse rates among individuals addicted to cocaine, 6 as well as with reduced craving in women with alcohol use disorder. 7 Initial attempts to harness these putative effects to reduce relapse rates were unsuccessful, as DHEA administration did not reduce relapse rates or craving among cocaine-dependent participants compared with placebo.…”

“…In recent years, accumulating evidence from preclinical and clinical studies suggest that administration of dehydroepiandrosterone (DHEA; an endogenous steroid hormone) during rehabilitation may lead to reduced relapse rates in SUD. In rodents, DHEA administration attenuated cocaine self-administration and decreased cocaine-seeking behaviors 3–5 . In humans, high levels of circulatory DHEA sulfate (DHEA-S) were associated with lower relapse rates among individuals addicted to cocaine, 6 as well as with reduced craving in women with alcohol use disorder 7 .…”