DHEA, a Neurosteroid, Decreases Cocaine Self-Administration and Reinstatement of Cocaine-Seeking Behavior in Rats

Doron, Ravid; Fridman, Lilach; Gispan-Herman, Iris; Maayan, Rachel; Weizman, Abraham; Yadid, Gal

doi:10.1038/sj.npp.1301013

Cited by 34 publications

(22 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The biopsychosocial model of challenge and threat may apply to the androgen DHEA in that the gain and loss framing instructions differentially impacted DHEA. We based the speculation that DHEA acted in line with reward cues largely on the literature on DHEA modulation of substance use seeking behaviors (Doron et al, 2006; Maayan et al, 2006), which tied this neurosteroid with reward-and motivation-related processes. Thus, while both DHEA and testosterone appeared stress-reactive, androgenic hormone rises may be driven by the motivation to complete a task and to successfully receive a performance-based incentive with the amount of intrinsic resources available to meet the expected demands.…”

Section: Discussionmentioning

confidence: 99%

Social evaluative threat with verbal performance feedback alters neuroendocrine response to stress

Phan

Schneider

Peres

et al. 2017

Hormones and Behavior

View full text Add to dashboard Cite

Laboratory stress tasks such as the Trier Social Stress Test (TSST) have provided a key piece to the puzzle for how psychosocial stress impacts the hypothalamic-pituitary-adrenal axis, other stress-responsive biomarkers, and ultimately wellbeing. These tasks are thought to work through biopsychosocial processes, specifically social evaluative threat and the uncontrollability heighten situational demands. The present study integrated an experimental modification to the design of the TSST to probe whether additional social evaluative threat, via negative verbal feedback about speech performance, can further alter stress reactivity in 63 men and women. This TSST study confirmed previous findings related to stress reactivity and stress recovery but extended this literature in several ways. First, we showed that additional social evaluative threat components, mid-task following the speech portion of the TSST, were still capable of enhancing the psychosocial stressor. Second, we considered stress-reactive hormones beyond cortisol to include dehydroepiandrosterone (DHEA) and testosterone, and found these hormones were also stress-responsive, and their release was coupled with one another. Third, we explored whether gain- and loss-framing incentive instructions, meant to influence performance motivation by enhancing the personal relevance of task performance, impacted hormonal reactivity. Results showed that each hormone was stress reactive and further had different responses to the modified TSST compared to the original TSST. Beyond the utility of showing how the TSST can be modified with heightened social evaluative threat and incentive-framing instructions, this study informs about how these three stress-responsive hormones have differential responses to the demands of a challenge and a stressor.

show abstract

Section: Discussionmentioning

confidence: 99%

Social evaluative threat with verbal performance feedback alters neuroendocrine response to stress

Phan

Schneider

Peres

et al. 2017

Hormones and Behavior

View full text Add to dashboard Cite

show abstract

“…However, others have shown that selective removal of the adrenal medulla fails to alter norepinephrine levels within the central nervous system (CNS) (Peskind et al, 1986). DHEA administration has been reported to reduce cocaine SA and reinstatement (Doron et al, 2006), but the adrenal glands do not appear to be the source of DHEA in the brain (Corpechot et al, 1981). Although it is unlikely that a loss of aldosterone would directly contribute to our observed effects, we cannot rule out an indirect contribution of mineralocorticoid actions as a consequence of altered electrolyte balance, despite our attempts to stabilize sodium concentrations in our ADX rats through inclusion of NaCl in their drinking water.…”

Section: Extinctionmentioning

confidence: 99%

Surgical Adrenalectomy with Diurnal Corticosterone Replacement Slows Escalation and Prevents the Augmentation of Cocaine-Induced Reinstatement in Rats Self-Administering Cocaine Under Long-Access Conditions

Mantsch

Baker

Serge

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

The loss of control over cocaine use and persistently heightened susceptibility to drug relapse that define human cocaine addiction are consequences of drug-induced neuroplasticity and can be studied in rats self-administering cocaine under conditions of daily long access (LgA) as escalating patterns of drug intake and heightened susceptibility to reinstatement. This study investigated the potential contribution of elevated glucocorticoids at the time of LgA cocaine self-administration (SA) to these behavioral indices of addictionrelated neuroplasticity. Rats provided 14 days of 6-h access (LgA) to cocaine showed a progressive escalation of SA and were more susceptible to cocaine-induced reinstatement (10 mg/kg, i.p.) compared to rats self-administering under short-access (ShA; 2 h) conditions. A surgical adrenalectomy and corticosterone replacement (ADX/C) regimen that eliminated SA-induced increases in corticosterone (CORT) while maintaining the diurnal pattern of secretion failed to alter SA or reinstatement in ShA rats but slowed escalation and attenuated later reinstatement in LgA rats when applied before but not after chronic LgA SA testing. Although the contribution of other adrenal hormones cannot be ruled out, these data suggest that elevated glucocorticoids at the time of cocaine exposure may be required for the effects of LgA SA on cocaine intake and later reinstatement. The inability of daily CORT administration before daily ShA SA, at a dose that reproduced the response during LgA SA, to mimic the effects of LgA SA suggests that elevated glucocorticoids during SA may play a permissive role in cocaine-induced neuroplasticity that contributes to addiction.

show abstract

“…Brain punches were extracted in absolute ethanol. Aliquots (200 ml) of the resulting ethanol solutions were completely evaporated and subjected to a commercially available DHEA radioimmunoassay (RIA) kit (Diagnostic Systems Laboratories, Webster, TX (Doron et al, 2006;Maayan et al, 2000). This RIA utilizes DHEA-DSL 9000 Activet coated tubes.…”

Section: Extraction Of Brain Tissue and Dhea Radioimmunoassaymentioning

confidence: 99%

DHEA Lessens Depressive-Like Behavior via GABA-ergic Modulation of the Mesolimbic System

Genud

Merenlender

Gispan-Herman

et al. 2008

Neuropsychopharmacol

Self Cite

View full text Add to dashboard Cite

Alterations in the levels of dehydroepiandrosterone (DHEA) in the brain can allosterically modulate g-aminobutyric-acid-type-A (GABA A R), N-methyl-D-aspartate (NMDAR), and Sigma-1 (s1R) receptors. In humans, DHEA has antidepressive effects; however, the mechanism is unknown. We examined whether alterations in DHEA also occur in an animal model of depression, the Flinders-sensitiveline (FSL) rats, with the intention of determining the brain site of DHEA action and its antidepressant mechanism. We discovered that DHEA levels were lower in some brain regions involved with depression of FSL rats compared to Sprague-Dawley (SD) controls. Moreover, DHEA (1 mg/kg IP for 14 days)-treated FSL rats were more mobile in the forced swim test than FSL controls. In the NAc and VTA, significant changes were observed in the levels of the d-subunit of GABA A , but not of s1R mRNA, in FSL rats compared to SD rats. The d-subunit controls the sensitivity of the GABA A R to the neurosteroid. Indeed, treatment (14 days) of FSL rats with the GABA A agonist muscimol (0.5 mg/kg), together with DHEA (a negative modulator of GABA A ), reversed the effect of DHEA on immobility in the swim test. Perfusion of DHEA sulfate (DHEAS) (3 nM and 30 nM for 14 days) into the VTA and NAc of FSL rats improved their performance in the swim test for at least 3 weeks post-treatment. Our results imply that alterations in DHEA are involved in the pathophysiology of depression and that the antidepressant action of DHEA is mediated via GABA A Rs in the NAc and VTA.

show abstract

DHEA, a Neurosteroid, Decreases Cocaine Self-Administration and Reinstatement of Cocaine-Seeking Behavior in Rats

Cited by 34 publications

References 20 publications

Social evaluative threat with verbal performance feedback alters neuroendocrine response to stress

Social evaluative threat with verbal performance feedback alters neuroendocrine response to stress

Surgical Adrenalectomy with Diurnal Corticosterone Replacement Slows Escalation and Prevents the Augmentation of Cocaine-Induced Reinstatement in Rats Self-Administering Cocaine Under Long-Access Conditions

DHEA Lessens Depressive-Like Behavior via GABA-ergic Modulation of the Mesolimbic System

Contact Info

Product

Resources

About