Dataset Information

Pregnenolone effects on provoked alcohol craving, anxiety, HPA axis, and autonomic arousal in individuals with alcohol use disorder.

ABSTRACT:

Rationale

Chronic alcohol intake down-regulates GABAergic transmission and reduces levels of neuroactive steroids. These changes are associated with greater stress dysregulation and high alcohol craving which in turn increases relapse risk.

Objectives

This study tested whether potentiation of the neurosteroid system with pregnenolone (PREG), a precursor to neuroactive steroids and known to increase GABAergic transmission, will normalize chronic alcohol-related stress adaptations in the hypothalamic-pituitary-adrenal (HPA) axis and autonomic responses and reduce alcohol craving to significantly impact relapse risk.

Methods

Forty-three treatment-seeking individuals with alcohol use disorder (AUD) were randomized to placebo (PBO) or supraphysiologic pregnenolone doses of 300 mg or 500 mg treatment using a parallel-between subject design as part of a larger 8-week pilot clinical trial. In week 2, they participated in a 3-day laboratory experiment where on each day they self-administered the assigned study drug in the laboratory and were then exposed to 5-min personalized guided imagery provocation of stress, alcohol, or neutral/relaxing cues, one condition per day on separate days, in a random, counterbalanced order. Repeated assessments of alcohol craving, anxiety, HPA axis, heart rate (HR), systolic (SBP), and diastolic blood pressure (DBP) and serum pregnenolone levels were made on each day.

Results

Pregnenolone levels were significantly increased in the PREG groups versus PBO. PREG treatment decreased stress- and alcohol cue- induced craving and dose-specifically reduced stress-induced anxiety in the 300 mg/day group. Both PREG doses compared to PBO also normalized CORT/ACTH and increased stress-induced HR, stress- and cue-induced SBP, and in the 300 mg PREG group cue-induced DBP responses relative to neutral condition.

Conclusions

Findings indicate that pregnenolone decreases stress- and alcohol cue-provoked craving and normalizes HPA axis and autonomic arousal in individuals with AUD, thereby supporting the need for further assessment of pregnenolone in the treatment of AUD.

SUBMITTER: Milivojevic V

PROVIDER: S-EPMC10630889 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pregnenolone effects on provoked alcohol craving, anxiety, HPA axis, and autonomic arousal in individuals with alcohol use disorder.

Milivojevic Verica V Sullivan Liam L Tiber Jessica J Fogelman Nia N Simpson Christine C Hermes Gretchen G Sinha Rajita R

Psychopharmacology 20221129 1

<h4>Rationale</h4>Chronic alcohol intake down-regulates GABAergic transmission and reduces levels of neuroactive steroids. These changes are associated with greater stress dysregulation and high alcohol craving which in turn increases relapse risk.<h4>Objectives</h4>This study tested whether potentiation of the neurosteroid system with pregnenolone (PREG), a precursor to neuroactive steroids and known to increase GABAergic transmission, will normalize chronic alcohol-related stress adaptations i ...[more]

PMID: 36445398

Similar Datasets

Project description:Research has demonstrated the positive association between alcohol craving and alcohol use and has identified craving as a central component of alcohol use disorders (AUD). Despite potential clinical implications, few studies have examined the relationship between craving and alcohol use in individuals with AUD and common psychiatric comorbidities or explored possible moderators of the craving-alcohol use relationship. The current study used daily monitoring data to: 1) replicate previous findings detecting a positive relationship between craving and alcohol use in individuals with AUD and co-occurring posttraumatic stress disorder (PTSD) and 2) extend these findings by examining the influence of initial change motivation on the craving-use relationship and within-day associations among craving, efforts to control craving, and alcohol consumption. Participants were 84 individuals with alcohol dependence and PTSD enrolled in an intervention study. Generalized estimating equations using pre-treatment baseline daily data revealed significant main effects for craving, craving control, and motivation to change alcohol use. Daily craving was positively related to alcohol use. Greater change motivation and craving control (i.e., efforts to resist craving, avoidance of thoughts and feelings related to craving) were negatively related to alcohol use. A significant interaction was detected between baseline change motivation and daily craving indicating that the association between craving and alcohol use was significantly stronger for those with low baseline change motivation. A significant interaction was also detected between craving control and daily craving, suggesting that participants were more likely to consume alcohol when experiencing high levels of craving if they reported low levels of craving control. Findings bolster the idea that efforts to prevent or ameliorate craving are critical to treatment success for individuals with AUD and PTSD who are seeking to reduce or quit drinking.

Project description:Prenatal alcohol exposure (PAE) is known to cause dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, including hyperresponsivity to stressors. Dysregulation of the HPA axis plays a role in vulnerability to stress-related disorders, such as anxiety and depression. Thus, the effects of PAE on HPA function may result in increased vulnerability to the effects of stress and, in turn, lead to the development of stress-related disorders. Indeed, individuals prenatally exposed to alcohol have an increased risk of developing anxiety and depression. However, it is unclear whether hypersecretion of corticosterone (CORT) in response to stress per se is involved with mediating differential effects of stress in PAE and control animals. To investigate the role of CORT in mediating effects of stress in both adult females and males following PAE, adrenalectomy with CORT replacement (ADXR) was utilized to produce similar CORT levels among prenatal treatment groups before exposure to chronic unpredictable stress (CUS). Anxiety-like behavior was evaluated using the open field and elevated plus maze, and depressive-like behavior was examined in the forced swim test. Mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNA expression was assessed in the medial prefrontal cortex (mPFC), amygdala, and hippocampal formation. Under the non-CUS condition, PAE alone differentially altered anxiety-like behavior in sham but not ADXR females and males, with females showing decreased anxiety-like behavior but males exhibiting increased anxiety-like behavior compared to their control counterparts. There were no effects of PAE alone on depressive-like in females or males. PAE also decreased GR mRNA expression in the hippocampal formation in females but had no effects on MR or GR mRNA expression in any brain region in males. CUS had differential effects on anxiety- and depressive-like behavior in PAE and control animals, and these effects were sex dependent. Importantly, ADXR unmasked differences between PAE and control animals, demonstrating that CORT may play a differential role in modulating behavior and HPA activity/regulation in PAE and control animals, and may do so in a sex-dependent manner.

Dataset Information

Pregnenolone effects on provoked alcohol craving, anxiety, HPA axis, and autonomic arousal in individuals with alcohol use disorder.

Rationale

Objectives

Methods

Results

Conclusions

Publications

Pregnenolone effects on provoked alcohol craving, anxiety, HPA axis, and autonomic arousal in individuals with alcohol use disorder.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets