M. Adrienne McGinn, Ph.D.

@article{pmid33647278,

title = {Glucocorticoid receptor modulators decrease alcohol self-administration in male rats},

author = {M Adrienne McGinn and Brendan J Tunstall and Joel E Schlosburg and Adriana Gregory-Flores and Olivier George and Giordano de Guglielmo and Barbara J Mason and Hazel J Hunt and George F Koob and Leandro F Vendruscolo},

url = {https://pubmed.ncbi.nlm.nih.gov/33647278/},

doi = {10.1016/j.neuropharm.2021.108510},

issn = {1873-7064},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Neuropharmacology},

volume = {188},

pages = {108510},

abstract = {Alcohol use disorder (AUD) is associated with the dysregulation of brain stress and reward systems, including glucocorticoid receptors (GRs). The mixed glucocorticoid/progesterone receptor antagonist mifepristone and selective GR antagonist CORT113176 have been shown to selectively reduce alcohol consumption in alcohol-dependent rats. Mifepristone has also been shown to decrease alcohol consumption and craving for alcohol in humans with AUD. The present study tested the effects of the GR modulators CORT118335, CORT122928, CORT108297, and CORT125134 on alcohol self-administration in nondependent (air-exposed) and alcohol-dependent (alcohol vapor-exposed) adult male rats. Different GR modulators recruit different GR-associated transcriptional cofactors. Thus, we hypothesized that these GR modulators would vary in their effects on alcohol drinking. CORT118335, CORT122928, and CORT125134 significantly reduced alcohol self-administration in both alcohol-dependent and nondependent rats. CORT108297 had no effect on alcohol self-administration in either group. The present results support the potential of GR modulators for the development of treatments for AUD. Future studies that characterize genomic and nongenomic effects of these GR modulators will elucidate potential molecular mechanisms that underlie alcohol drinking in alcohol-dependent and nondependent states.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33005820,

title = {Chronic inflammatory pain alters alcohol-regulated frontocortical signaling and associations between alcohol drinking and thermal sensitivity},

author = {M Adrienne McGinn and Kimberly N Edwards and Scott Edwards},

url = {https://pubmed.ncbi.nlm.nih.gov/33005820/},

doi = {10.1016/j.ynpai.2020.100052},

issn = {2452-073X},

year  = {2020},

date = {2020-09-15},

journal = {Neurobiol Pain},

volume = {8},

pages = {100052},

abstract = {Alcohol use disorder (AUD) is a chronic, relapsing psychiatric disorder that is characterized by the emergence of negative affective states. The transition from recreational, limited intake to uncontrolled, escalated intake is proposed to involve a transition from positive to negative reinforcement mechanisms for seeking alcohol. Past work has identified the emergence of significant hyperalgesia/allodynia in alcohol-dependent animals, which may serve as a key negative reinforcement mechanism. Chronic pain has been associated with enhanced extracellular signal-regulated kinase (ERK) activity in cortical and subcortical nociceptive areas. Additionally, both pain and AUD have been associated with increased activity of the glucocorticoid receptor (GR), a key mediator of stress responsiveness. The objectives of the current study were to first determine relationships between thermal nociceptive sensitivity and alcohol drinking in male Wistar rats. While inflammatory pain induced by complete Freund's adjuvant (CFA) administration did not modify escalation of home cage drinking in animals over four weeks, the relationship between drinking levels and hyperalgesia symptoms reversed between acute (1 week) and chronic (3-4 week) periods post-CFA administration, suggesting that either the motivational or analgesic effects of alcohol may be altered over the time course of chronic pain. We next examined ERK and GR phosphorylation in pain-related brain areas (including the central amygdala and prefrontal cortex subregions) in animals experiencing acute withdrawal from binge alcohol administration (2 g/kg, 6 h withdrawal) and CFA administration (four weeks) to model the neurobiological consequences of binge alcohol exposure in the context of pain. We observed a significant interaction between alcohol and pain state, whereby alcohol withdrawal increased ERK phosphorylation across all four frontocortical areas examined, although this effect was absent in animals experiencing chronic inflammatory pain. Alcohol withdrawal also increased GR phosphorylation across all four frontocortical areas, but these changes were not altered by CFA. Interestingly, we observed significant inter-brain regional correlations in GR phosphorylation between the insula and other regions investigated only in animals exposed to both alcohol and CFA, suggesting coordinated activity in insula circuitry and glucocorticoid signaling in this context. The results of these studies provide a greater understanding of the neurobiology of AUD and will contribute to the development of effective treatment strategies for comorbid AUD and pain.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Vendruscolo:2015kt,

title = {Glucocorticoid receptor antagonism decreases alcohol seeking in alcohol-dependent individuals.},

author = {Leandro F Vendruscolo and David Estey and Vivian Goodell and Lauren G Macshane and Marian L Logrip and Joel E Schlosburg and Adrienne M McGinn and Eva R Zamora-Martinez and Joseph K Belanoff and Hazel J Hunt and Pietro P Sanna and Olivier George and George F Koob and Scott Edwards and Barbara J Mason},

url = {https://pubmed.ncbi.nlm.nih.gov/26121746/},

doi = {10.1172/JCI79828},

year  = {2015},

date = {2015-08-03},

urldate = {2015-08-03},

journal = {J Clin Invest},

volume = {125},

number = {8},

pages = {3193-3197},

abstract = {Alcoholism, or alcohol use disorder, is a major public health concern that is a considerable risk factor for morbidity and disability; therefore, effective treatments are urgently needed. Here, we demonstrated that the glucocorticoid receptor (GR) antagonist mifepristone reduces alcohol intake in alcohol-dependent rats but not in nondependent animals. Both systemic delivery and direct administration into the central nucleus of the amygdala, a critical stress-related brain region, were sufficient to reduce alcohol consumption in dependent animals. We also tested the use of mifepristone in 56 alcohol-dependent human subjects as part of a double-blind clinical and laboratory-based study. Relative to placebo, individuals who received mifepristone (600 mg daily taken orally for 1 week) exhibited a substantial reduction in alcohol-cued craving in the laboratory, and naturalistic measures revealed reduced alcohol consumption during the 1-week treatment phase and 1-week post-treatment phase in mifepristone-treated individuals. Mifepristone was well tolerated and improved liver-function markers. Together, these results support further exploration of GR antagonism via mifepristone as a therapeutic strategy for alcoholism.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}