The effect of DHEA complementary treatment on heroin addicts participating in a rehabilitation program: a preliminary study.

We evaluated the effect of DHEA complementary treatment in opiate addicts undergoing detoxification. DHEA (100 mg/day) or placebo was added to the routine medication protocol in a randomized, double blind controlled study. Follow-up for 12 months was conducted. Two separate DHEA-treated subgroups were identified by the Fuzzy clustering method: one showed statistically significant improvement in the severity of withdrawal symptoms, depression and anxiety scores (n=34; p<0.001 for all) and the other subgroup deteriorated in all measures (n=15). DHEA at the end of the detoxification program showed a tendency towards correlation with the duration of abstinence (r=0.6843; p>0.05; n=6), while a negative correlation was obtained with the cortisol level (r=-0.900; p=0.005, n=8). The completion-rate of the DHEA-improved subgroup was greater than in the DHEA-deteriorated subgroup (64.7% vs. 33.3%, respectively). The influence of supplementary DHEA treatment was mostly effective in heroin addicts who had not previously used either cocaine or benzodiazepines and who had experienced only few withdrawal programs.

Decreased circulatory levels of neuroactive steroids in behaviourally more extremely affected rats subsequent to exposure to a potentially traumatic experience.

This study examined the effects of stress exposure on plasma levels of corticosterone, dehydroepiandrosterone (DHEA) and its sulphate derivative DHEA-S in relation to behavioural responses. The magnitude of anxiety-like behaviours on the elevated plus-maze and of non-habituated exaggerated startle reactions were assessed in rats exposed to stress compared to controls. Individuals displaying extreme behavioural changes were termed extreme behavioural response (EBR), as opposed to minimal behavioural response (MBR) in both paradigms performed consecutively. Significantly increased circulating corticosterone levels and decreased DHEA levels were found 7 d post-exposure only in EBR individuals, not in their MBR counterparts. DHEA-S levels were reduced in both EBR and MBR stress-exposed rats compared to controls. This suggests that concomitantly decreased circulatory levels of DHEA and elevated corticosterone levels may be associated with an extreme (pathological) response to stress, whilst maintenance of normal levels of both steroids may be associated with minimal response, denoting resilience.

The protective effect of frontal cortex dehydroepiandrosterone in anxiety and depressive models in mice.

We aimed to verify whether DHEA, a neuoroactive neurosteroid, has a protective role in preventing the occurrence or enhancement of the severity of depression and anxiety in mice. Four groups were tested: controls, mice possessing significantly high frontal cortex DHEA levels, achieved by repeated DHEA injections (1.6 mg/Kg, i.p.), mice that have significantly low frontal cortex DHEA levels, consequent to castration and mice possessing significantly low frontal cortex DHEA levels, treated with DHEA to reverse its level to normal, achieved by castration and repeated DHEA injections (0.4 mg/Kg, i.p.). The Forced Swim Test to determine depressive-like and the Elevated Plus Maze (EPM) to evaluate anxiety-like behaviors, were used. We found that DHEA had an anti-depressive-like effect, as shown by a decreased immobility time in mice possessing a high level of frontal cortex DHEA and increased immobility time in mice that have a low frontal cortex DHEA level. DHEA also demonstrated an anti-anxiety-like effect, as shown by the open-arm time in EPM, which correlated with DHEA level. Mice with significantly low DHEA levels when restored to normal, did not differ from controls. In conclusion, high levels of DHEA have an anti-anxiety-like and an anti-depressive-like effect in mice and those with low levels of frontal cortex DHEA are more vulnerable to depression and/or anxiety.

Is brain dehydroepiandrosterone synthesis modulated by free radicals in mice?

Dehydroepiandrosterone (DHEA) is a neurosteroid synthesized de novo in the brain, in addition to the periphery, modulating some membrane, ion-gated channel neurotransmitter receptors. P450-17alpha-hydroxylase activity converting pregnenolone to DHEA, has not yet been identified in the brain of rodents. Studies in brain-derived primary cultures and cell lines, suggest a possible alternative pathway for DHEA synthesis involving oxygenated hydroxyperoxides. We investigated DHEA synthesis in the brains of castrated male mice before and after treatment with N-acetylcysteine amide (AD4) (a newly developed brain penetrating antioxidant). We found a significant increase in brain DHEA level 24 h after castration, which was totally blocked by AD4. This blockade of castration-induced increased brain DHEA synthesis, supports the assumption that this synthesis may also be affected by free radicals. This is the first in vivo study indicating the possible existence of an in-brain oxidative stress-related pathway leading to brain DHEA production.