Clyde Hodge, Ph.D.
Department of Psychiatry
Bowles Center for Alcohol Studies
Office | 3019A Thurston-Bowles Bldg, CB#7178
Email | email@example.com
Lab Website |
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.
Mining the nucleus accumbens proteome for novel targets of alcohol self-administration in male C57BL/6J mice. Faccidomo S, Swaim KS, Saunders BL, Santanam TS, Taylor SM, Kim M, Reid GT, Eastman VR, Hodge CW. Psychopharmacology. 2018; 235(6):1681-1696. NIHMSID: NIHMS947885 PubMed [journal] PMID: 29502276, PMC5949261
Cue-induced reinstatement of alcohol-seeking behavior is associated with increased CaMKII T286 phosphorylation in the reward pathway of mice. Salling MC, Hodge CJ, Psilos KE, Eastman VR, Faccidomo SP, Hodge CW Pharmacology, biochemistry, and behavior. 2017; 163:20-29. NIHMSID: NIHMS935215 PubMed [journal] PMID:29100991
Potentiation of amygdala AMPA receptor activity selectively promotes escalated alcohol self-administration in a CaMKII-dependent manner. Cannady R, Fisher KR, Graham C, Crayle J, Besheer J, Hodge CW. Addiction biology. 2017; 22(3):652-664. NIHMSID: NIHMS748206 PubMed [journal] PMID: 26742808