Faculty & Research

Clyde Hodge, Ph.D.

Professor
Department of Psychiatry and Bowles Center for Alcohol Studies

Office | 1025A Thurston-Bowles Bldg, CB#7178

Email | chodge@med.unc.edu

Lab Website | Hodge Lab

Research Interests

Alcoholism is a complex neuropsychiatric disorder that is characterized by recurring cycles of chronic drinking, abstinence and relapse.  Emerging evidence suggests that alcohol and other drugs of abuse may produce maladaptive changes in a variety of neurotransmitter, cell signaling and gene transcription pathways that lead to enduring changes in brain structure and function.  These neuroadaptations are thought to regulate behavioral pathologies that occur in alcoholism. 

The primary goals of our research are to 1) elucidate neuroadaptations in molecular signaling pathways associated with chronic voluntary alcohol drinking and abstinence; and 2) investigate the functional involvement of these molecular pathways in the behavioral effects of alcohol including self-administration, mood regulation (i.e., anxiety and depression), discrimination, and sensitization.  Understanding the molecular mechanisms of drug-induced plasticity in brain and behavioral functions is of potential importance for development of new pharmacotherapies for problems associated with alcoholism, such as relapse.

Research Projects

Molecular Mechanisms of Ethanol Reinforcement
R01 AA014983; Hodge (PI)
The primary goal of this application is to characterize the involvement of metabotropic glutamate receptors in alcohol's reinforcing effects.
Molecular Mechanisms of Alcohol Drinking and Relapse
P60 AA011605; Component of UNC-CH Center Grant; Crews (PI), Hodge (Component PI)
This component of the NIAAA Alcohol Center Grant is focused on elucidating the functional involvement of the cell signaling pathways in alcohol drinking and relapse.  Studies are focused on protein kinase C isoforms, the ERK/MAPK pathway, and how changes in activity of these kinases regulate alcohol drinking, relapse, and reinforcement.   
Behavioral and Molecular Mechanisms of Ethanol-Induced Depression
R01 AA16629; Hodge (PI)
We have discovered that abstinence from chronic alcohol drinking is associated with increased depression-like behavior in mice.  The goals of this multidisciplinary project are to identify molecular mechanisms of this alcohol-induced increase in depression. 

Mentored Research Projects

Novel Mechanism of Ethanol Discrimination
K01 AA016009; Dr. Joyce Besheer (PI), Hodge (Mentor)
The primary goal of this project is to characterize neurobiological mechanisms of the subjective (i.e., discriminative) effects of alcohol.
Characterization of Adolescent Ethanol Sensitization
F31 AA016032; Rebekah Stevenson (PI), Hodge (Mentor)
The objective of this pre-doctoral research project is to examine developmental differences in neurobehavioral adaptation to repeated ethanol.
Ethanol Drinking, Depression, and Neurogenesis
F31 AA016043; Jennifer Hillmann (PI), Hodge (Mentor)
This pre-doctoral project is examining the effects of alcohol drinking on depression-like behavior with an emphasis on adult hippocampal neurogenesis as a potential mechanism. 

Center Line Articles

• It's in the Molecules: Hodge Laboratory Elucidates Subcellular Mechanisms of Alcohol Dependence (Vol 21, No. 1, 2010)

• Hodge Lab Makes New Strides in Understanding the Molecular and Cellular Basis of Alcohol Reinforcement (Vol 17, No. 3, 2006)

• Keys to Addiction Found in Brain Reward Systems (Vol 13, No.2, 2002)

Recent Publications

Click for a list of publications from PubMed

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.

CRF-1 antagonist and CRF-2 agonist decrease binge-like ethanol drinking in C57BL/6J mice independent of the HPA axis.  Lowery EG, Spanos M, Navarro M, Lyons AM, Hodge CW, Thiele TE.  Neuropsychopharmacology. 2010 May;35(6):1241-52.

Metabotropic glutamate receptor 5 activity in the nucleus accumbens is required for the maintenance of ethanol self-administration in a rat genetic model of high alcohol intake.  Besheer J, Grondin JJ, Cannady R, Sharko AC, Faccidomo S, Hodge CW.  Biol Psychiatry. 2010 May 1;67(9):812-22.

Alcohol, cocaine, and brain stimulation-reward in C57Bl6/J and DBA2/J mice. Fish EW, Riday TT, McGuigan MM, Faccidomo S, Hodge CW, Malanga CJ. Alcohol Clin Exp Res. 2010 Jan;34(1):81-9.

Suppression of heavy drinking and alcohol seeking by a selective ALDH-2 inhibitor.  Arolfo MP, Overstreet DH, Yao L, Fan P, Lawrence AJ, Tao G, Keung WM, Vallee BL, Olive MF, Gass JT, Rubin E, Anni H, Hodge CW, Besheer J, Zablocki J, Leung K, Blackburn BK, Lange LG, Diamond I. Alcohol Clin Exp Res. 2009 Nov;33(11):1935-44.

Increased operant responding for ethanol in male C57BL/6J mice: specific regulation by the ERK1/2, but not JNK, MAP kinase pathway. Faccidomo S, Besheer J, Stanford PC, Hodge CW. Psychopharmacology (Berl). 2009 May;204(1):135-47.

Besheer J, Schroeder JP, Stevenson RA, Hodge CW. Ethanol-induced alterations of c-Fos immunoreactivity in specific limbic brain regions following ethanol discrimination training.Brain Res. 2008 Sep 26;1232:124-31

Schroeder JP, Spanos M, Stevenson JR, Besheer J, Salling M, Hodge CW. Cue-induced reinstatement of alcohol-seeking behavior is associated with increased ERK1/2 phosphorylation in specific limbic brain regions: blockade by the mGluR5 antagonist MPEP.Neuropharmacology. 2008 Sep;55(4):546-54.

Salling MC, Faccidomo S, Hodge CW.  Nonselective suppression of operant ethanol and sucrose self-administration by the mGluR7 positive allosteric modulator AMN082.Pharmacol Biochem Behav. 2008 Nov;91(1):14-20.

Stevenson JR, Schroeder JP, Nixon K, Besheer J, Crews FT, Hodge CW. Abstinence following Alcohol Drinking Produces Depression-Like Behavior and Reduced Hippocampal Neurogenesis in Mice.Neuropsychopharmacology. 2008 Jun 18.