Department of Psychiatry
Bowles Center for Alcohol Studies
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.
A major focus of our work is on understanding how alcohol alters neural processes to gain control over the individual via alterations of positive reinforcement mechanisms. Using rodent models, we have identified specific neural systems that regulate alcohol-seeking behavior and evaluate co-morbid neuropsychiatric conditions such as anxiety and depression. Recently, we have utilized unbiased high-throughput proteomic screens, to discover the spectrum of neural proteins that are altered by alcohol use by adults and adolescents. Protein targets in specific brain regions are validated for functional involvement in alcohol self-administration using site-specific microinjection strategies. At the mechanistic level, our studies have identified glutamate-linked receptors (e.g., NMDA, mGluR5, AMPA) and associated signaling pathways (e.g., PKC, ERK, CaMKII) as key targets of that regulate alcohol reinforcement. Recently, we have incorporated optogenetics and electrophysiological measures in our studies via training and collaboration within the UNC Alcohol Center Core, of which Dr. Hodge is the Director. By delineating how alcohol alters protein networks that, in turn, regulate drug-seeking behavior, we hope to elucidate novel neural mechanisms that influence the development of addiction.
- It's in the Molecules: Hodge Laboratory Elucidates Subcellular Mechanisms of Alcohol Dependence
- Hodge Lab Makes New Strides in Understanding the Molecular and Cellular Basis of Alcohol Reinforcement
- Keys to Addiction Found in Brain Reward Systems
- Agoglia AE, Holstein SE, Reid G, Hodge CW. CaMKIIα-GluA1 activity underlies vulnerability to adolescent binge alcohol drinking. Alcohol Clin Exp Res, [Epub ahead of print], 6/16/2015. PMID: 26247621
- Faccidomo S, Salling MC, Galunas C, Hodge CW. Pharmacological inhibition of extracellular-signal regulated protein kinase (ERK) in the prefrontal cortex, nucleus accumbens and amygdala of C57BL/6J mice: differential effects on ethanol self-administration. Psychopharmacology 232(18):3417-30; 2015. PMID: 26123321
- Salling MC, Faccidomo SP, Li C, Psilos K, Galunas C, Spanos M, Agoglia AE, Kash TL, Hodge CW. Moderate alcohol drinking and the amygdala proteome: Identification and validation of CaMKII as a novel molecular mechanism of the positive reinforcing effects of alcohol. Biological Psychiatry, [Epub ahead of print]; 2014. PMID: 25579851
- Agoglia AE, Sharko AC, Psilos KE, Holstein SE, Reid GT, Hodge CW. Alcohol Alters the Activation of ERK1/2, a Functional Regulator of Binge Alcohol Drinking in Adult C57BL/6J Mice. Alcohol: Clin Exp Res 39(3):463-75; 2015. PMID: 25703719
- Cook J, Werner D. Maldonado-Devincci A, Leonard M, Fisher K, O'Buckley T, Porcu P, McCown T, Besheer J, Hodge CW, Morrow AL. Overexpression of the steroidogenic enzyme cytochrome P450 side chain cleavage in the ventral tegmental area increases 3α,5α-THP and reduces long-term operant ethanol self-administration. Journal of Neuroscience 34(17):5824-34; 2014. PMID: 24760842