Neurosteroid and Ethanol Interactions (MERIT Award):
The major goal of this project is to investigate the role of neuroactive steroids in ethanol action, tolerance and dependence.
Mechanisms of Addiction Pathogenesis
The major goal of this project is to determine the molecular mechanisms that underlie chronic ethanol-induced adaptations of GABA-A receptors in brain and cultured cerebral cortical neurons.
Stress, Alcohol and GABAergic Neuroactive Steroids:
The objective of this project is to elucidate the role of neuroactive steroids in the link between stress and excessive alcohol intake, including studies of neuroadaptive changes caused by chronic alcohol exposure.
Center Line Articles
Click here for a full list of publications from PubMed
Ethanol Activation of Protein Kinase A Regulates GABA(A) Receptor Subunit Expression in the Cerebral Cortex and Contributes to Ethanol-Induced Hypnosis. Kumar S, Ren Q, Beckley JH, O'Buckley TK, Gigante ED, Santerre JL, Werner DF, Morrow AL. Front Neurosci. 2012;6:44. Epub 2012 Apr 9.
A history of depression in women is associated with an altered GABAergic neuroactive steroid profile. Girdler SS, Lindgren M, Porcu P, Rubinow DR, Johnson JL, Morrow AL. Psychoneuroendocrinology. 2012 Apr;37(4):543-53.
Genetic analysis of the neurosteroid deoxycorticosterone and its relation to alcohol phenotypes: identification of QTLs and downstream gene regulation. Porcu P, O'Buckley TK, Song SC, Harenza JL, Lu L, Wang X, Williams RW, Miles MF, Morrow AL. PLoS One. 2011 Apr 8;6(4):e18405.
PKCγ is required for ethanol-induced increases in GABA(A) receptor α4 subunit expression in cultured cerebral cortical neurons. Werner DF, Kumar S, Criswell HE, Suryanarayanan A, Fetzer JA, Comerford CE, Morrow AL. J Neurochem. 2011 Feb;116(4):554-63. doi: 10.1111/j.1471-4159.2010.07140.x. Epub 2011 Jan 19.
Pregnenolone and ganaxolone reduce operant ethanol self-administration in alcohol-preferring p rats. Besheer J, Lindsay TG, O'Buckley TK, Hodge CW, Morrow AL. Alcohol Clin Exp Res. 2010 Dec;34(12):2044-52. doi: 10.1111/j.1530-0277.2010.01300.x. Epub 2010 Oct 14.
Chronic ethanol exposure produces tolerance to elevations in neuroactive steroids: mechanisms and reversal by exogenous ACTH. Boyd KN, Kumar S, O'Buckley TK, Morrow AL. J Neurochem. 2010 Oct;115(1):142-52.
Naltrexone selectively elevates GABAergic neuroactive steroid levels in heavy drinkers with the Asp40 allele of the OPRM1 gene: a pilot investigation. Ray LA, Hutchison KE, Ashenhurst JR, Morrow AL. Alcohol Clin Exp Res. 2010 Aug;34(8):1479-87.
Ethanol reduces GABAA alpha1 subunit receptor surface expression by a protein kinase Cgamma-dependent mechanism in cultured cerebral cortical neurons. Kumar S, Suryanarayanan A, Boyd KN, Comerford CE, Lai MA, Ren Q, Morrow AL. Mol Pharmacol. 2010 May;77(5):793-803.
Ethanol induction of steroidogenesis in rat adrenal and brain is dependent upon pituitary ACTH release and de novo adrenal StAR synthesis. Boyd KN, Kumar S, O'Buckley TK, Porcu P, Morrow AL. J Neurochem. 2010 Feb;112(3):784-96.
The effects of acute and chronic ethanol exposure on presynaptic and postsynaptic gamma-aminobutyric acid (GABA) neurotransmission in cultured cortical and hippocampal neurons. Fleming RL, Manis PB, Morrow AL. Alcohol. 2009 Dec;43(8):603-18.