Early life stress is a risk factor for excessive alcohol drinking and impulsivity in adults and is mediated via a CRF/GABAA mechanism

Autor: Marjorie C. Gondré-Lewis, Kaitlin T. Warnock, Hong Wang, Harry L. June, Kimberly A. Bell, Holger Rabe, Veera Venkata Naga Phani Babu Tiruveedhula, James Cook, Hartmut Lüddens, Laure Aurelian
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Corticotropin-Releasing Hormone
Physiology
Self Administration
Rats
Sprague-Dawley
Behavioral Neuroscience
0302 clinical medicine
GABA receptor
Risk Factors
Antalarmin
Prefrontal cortex
GABAA receptor
Maternal Deprivation
Amygdala
Vitamin B 12
Psychiatry and Mental health
Neuropsychology and Physiological Psychology
medicine.anatomical_structure
Female
medicine.symptom
Psychology
medicine.drug
Clinical psychology
medicine.medical_specialty
Alcohol Drinking
medicine.drug_class
Prefrontal Cortex
Binge drinking
Impulsivity
Receptors
Corticotropin-Releasing Hormone
Article
03 medical and health sciences
Internal medicine
medicine
Animals
Pyrroles
Benzodiazepine
Ethanol
Endocrine and Autonomic Systems
Receptors
GABA-A
Rats
Pyrimidines
030104 developmental biology
Endocrinology
Impulsive Behavior
Conditioning
Operant
Stress
Psychological
030217 neurology & neurosurgery
Zdroj: Stress. 19:235-247
ISSN: 1607-8888
1025-3890
DOI: 10.3109/10253890.2016.1160280
Popis: Childhood stress and trauma are associated with substance use disorders in adulthood, but the neurological changes that confer increased vulnerability are largely unknown. In this study, maternal separation (MS) stress, restricted to the pre-weaning period, was used as a model to study mechanisms of protracted effects of childhood stress/traumatic experiences on binge drinking and impulsivity. Using an operant self-administration model of binge drinking and a delay discounting assay to measure impulsive-like behavior, we report that early life stress due to MS facilitated acquisition of binge drinking and impulsivity during adulthood in rats. Previous studies have shown heightened levels of corticotropin releasing factor (CRF) after MS, and here, we add that MS increased expression levels of GABA(A) α2 subunit in central stress circuits. To investigate the precise role of these circuits in regulating impulsivity and binge drinking, the CRF1 receptor antagonist antalarmin and the novel GABA(A) α2 subunit ligand 3-PBC were infused into the central amygdala (CeA) and medial prefrontal cortex (mPFC). Antalarmin and 3-PBC at each site markedly reduced impulsivity and produced profound reductions on binge-motivated alcohol drinking, without altering responding for sucrose. Furthermore, whole-cell patch-clamp studies showed that low concentrations of 3-PBC directly reversed the effect of relatively high concentrations of ethanol on α2β3γ2 GABA(A) receptors, by a benzodiazepine site-independent mechanism. Together, our data provide strong evidence that maternal separation, i.e. early life stress, is a risk factor for binge drinking, and is linked to impulsivity, another key risk factor for excessive alcohol drinking. We further show that pharmacological manipulation of CRF and GABA receptor signaling is effective to reverse binge drinking and impulsive-like behavior in MS rats. These results provide novel insights into the role of the brain stress systems in the development of impulsivity and excessive alcohol consumption.
Databáze: OpenAIRE
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