Current CTNA Projects:
Neural mechanisms linking the responses to incentive stimuli to the formation and expression of ethanol-related habits
Principal Investigator: Dr. Jane Taylor. This project is a microcosm of the entire CTNA, conducting studies in animals that articulate mechanisms central to each project that could not be explicitly tested in humans. These studies will identify neurobehavioral mechanisms underlying vulnerability to habitual alcohol- seeking behavior and relapse.
Principal Investigators: Dr. Anissa Abi-Dargham & Dr. Ismene Petrakis. CTNA will test the central hypothesis that the heritable risk for alcoholism reflects dysfunction of cortico-striatal-midbrain circuitry, mediated by the interplay of glutamate and dopamine, that biases people to respond to drug-like rewards relative to delayed reward/punishments. This bias to respond to drug-like rewards leads to enhanced learning of alcohol-related associations, and facilitation of the development of habitual alcohol consumption. This project will test this hypothesis by assessing alcohol induced dopamine (DA) release in the striatum in at risk subjects and in patients with alcoholism to demonstrate that risk is associated with an increased alcohol-induced DA release in the striatum while the transition from risk to habit is associated with a decreased response. Thus DA dysregulation in ventral striatum influences the propensity to become addicted, and is altered by the process of addiction.
Functional neuroimaging of alcoholism vulnerability: glutamate, reward, and Pavlovian-to-Instrumental Transfer
Principal Investigator: Dr. Godfrey Pearlson. This project will clarify the neurobiology of various forms of impulsivity and disordered reward mechanisms seen in individuals at risk for alcoholism. In particular it will use pharmacologic probes of the NMDA system to explore NMDA/DA interactions in the ventral striatum in a series of fMRI tasks related to reward to assess the relevant circuitry related to the above questions.
Principal Investigator: Dr. Suchitra Krishnan-Sarin. This project extends hypotheses from Projects 1-3 and builds on exciting preliminary findings from prior CTNA projects using our alcohol self-administration paradigm. In CTNA-1, we observed that naltrexone reduced drinking in drinkers with a family history of alcoholism (FHP), but not in family-history negative (FHN) drinkers, with no significant reductions in the stimulatory effects of alcohol or alcohol craving in either group. In CTNA-2, memantine reduced the stimulatory effects of alcohol and alcohol craving, with trends towards reduction in drinking in FHP, but not FHN drinkers, in this ongoing study. In the current CTNA project, we will conduct a "proof of concept" evaluation in FHP drinkers of whether naltrexone and memantine have synergistic effects on reducing alcohol effects, alcohol craving, and alcohol drinking.
Director: Dr. Joel Gelernter. The goal of the Genetics Core is to support the genetic components of each of the projects participating in this Center to help understand the nature of genetic influences on the phenotypes measured, and to allow for the ascertainment of genetic covariates that might affect those outcomes.
Director:Dr. Kelly S. DeMartini. The CTNA places a high priority on maintaining an efficient flow of information in order to promote the safe and successful completion of proposed studies, to support the initiation of novel pilot studies, to facilitate the career development of trainees and junior faculty affiliated with the Center, and to promote the dissemination of research advances.
Director: Dr. John Krystal. The Pilot Projects Core provides a mechanism to initiate small-scale investigations that implement new technologies or to test important hypotheses associated with the CTNA mission. These projects serve the CTNA by 1) testing hypotheses or addressing methodologic issues central to the CTNA, 2) bringing new investigators into the CTNA and the field of alcoholism research, 3) generating new alcoholism RO1’s, 4) enabling CTNA to rapidly adapt to advances in the field, and 5) guiding the next iteration of the CTNA. Pilot Project Proposals are solicited through an open and public solicitation process. Proposal are developed in collaboration with the CTNA Cores (Data Management and Biostatistics, Clinical, Genetics) and refined with feedback from the Executive Committee.