A. Leslie Morrow, Ph.D.

Email: leslie_morrow@med.unc.edu

Office Phone: (919) 966-7682

Website: www.med.unc.edu/alcohol/molneuro.html


Education:

B.S., Psychobiology, University of California, Davis

Ph.D., Neuroscience, University of California, San Diego

Post Doctoral Fellowship, Molecular Neuropharmacology, National Institute of Mental Health

Summary Statement:

Dr. Morrow's laboratory is engaged in studies of the function, expression, regulation and molecular biology of GABA receptors in the CNS. They are particularly interested in the molecular mechanisms that underlie the effects of acute and chronic ethanol consumption, including the development of tolerance and dependence. They are studying the regulation of GABA receptors to determine whether alterations in the expression of these receptors could account for CNS hyperexcitability following ethanol withdrawal. They have shown that chronic exposure to ethanol and barbiturates alters the function and expression of certain types of GABA receptors, such that these receptors are less sensitive to GABA and the drugs themselves. These mechanisms could account for the development of tolerance to their behavioral effects. They are probing the biochemical mechanisms that control GABA receptor function and expression in the brain. Dr. Morrow's laboratory is investigating which subtypes of GABA receptors in the brain are sensitive to these drugs and whether GABA receptor subtype gene expression is modified by chronic alcohol and drug exposure. An understanding of how this receptor is regulated could lead to rational and creative new therapies for alcoholism and drug abuse.


Representative Publications:

1. 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.
2. 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.
3. The role of neuroactive steroids in ethanol/stress interactions: proceedings of symposium VII at the Volterra conference on alcohol and stress, Morrow AL, Biggio G, Serra M, Becker HC, Lopez MF, Porcu P, Alward SE, O'Buckley TK. Alcohol. 2009 Nov;43(7):521-30.
4. The role of GABA(A) receptors in the acute and chronic effects of ethanol: a decade of progress. Kumar S, Porcu P, Werner DF, Matthews DB, Diaz-Granados JL, Helfand RS, Morrow AL. Psychopharmacology (Berl). 2009 Sep;205(4):529-64.
5. Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia. Marx CE, Keefe RS, Buchanan RW, Hamer RM, Kilts JD, Bradford DW, Strauss JL, Naylor JC, Payne VM, Lieberman JA, Savitz AJ, Leimone LA, Dunn L, Porcu P, Morrow AL, Shampine LJ. Neuropsychopharmacology. 2009 Jul;34(8):1885-903.
6. Simultaneous quantification of GABAergic 3alpha,5alpha/3alpha,5beta neuroactive steroids in human and rat serum. Porcu P, O'Buckley TK, Alward SE, Marx CE, Shampine LJ, Girdler SS, Morrow AL. Steroids. 2009 Apr-May;74(4-5):463-73.
7. Boyd KN, O'Buckley TK, Morrow AL. Role of acetaldehyde in ethanol-induced elevation of the neuroactive steroid 3alpha-hydroxy-5alpha-pregnan-20-one in rats.Alcohol Clin Exp Res. 2008 Oct;32(10):1774-81.