AUTHOR=Rabat Yolaine , Henkous Nadia , Corio Marc , Nogues Xavier , Beracochea Daniel 

TITLE=Baclofen but Not Diazepam Alleviates Alcohol-Seeking Behavior and Hypothalamic–Pituitary–Adrenal Axis Dysfunction in Stressed Withdrawn Mice

JOURNAL=Frontiers in Psychiatry

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2019.00238

DOI=10.3389/fpsyt.2019.00238

ISSN=1664-0640

ABSTRACT=This study compares the impact of repeated injections of baclofen (an agonist of GABAB receptors) or diazepam (a benzodiazepine having an agonist action on GABAA receptors) given during the alcohol-withdrawal period on the stress-induced restoration of alcohol-seeking behavior and HPA axis dysfunction after a long (4 weeks) abstinence. Thus, C57BL/6 mice were submitted to a 6-month alcohol consumption (12%v/v) and were progressively withdrawn to water before testing. Diazepam (Valium®, Roche) and baclofen (Baclofen®, Mylan) were administered intraperitoneally for 15 consecutive days (1 injection/day) during the withdrawal period at decreasing doses ranged from 1.0mg/kg (Day-15) to 0.25 mg/kg (Day-1) for diazepam and from 1.5mg/kg (Day-15) to 0.37mg/kg (Day-1) for baclofen. Alcohol-seeking behavior was evaluated by alcohol-place preference in an odor recognition task. In stress condition, mice received 3 electric footshocks 45 minutes before behavioral testing. Blood was sampled immediately after behavioral testing and plasma corticosterone concentrations were measured by commercial Enzyme Immunoassay kits. Results showed that non-stressed withdrawn mice did not exhibit alcohol-place preference nor alteration of plasma corticosterone concentrations relative to water-controls. After stress however, withdrawn-mice exhibited a significant alcohol-place preference and higher circulating corticosterone concentrations as compared to stressed water-controls. Interestingly, repeated administration during the withdrawal phase of baclofen but not diazepam suppressed both the alcohol-place preference and normalized corticosterone levels in stressed withdrawn animals. In conclusion, this study evidences that a pre-treatment with baclofen but not with diazepam during the withdrawal phase normalized, even after a long period of abstinence, the HPA axis response to stress, which contributes to the long-term preventing effects of this compound on alcohol-seeking behavior.