Alcoholism; Brain; Neurobiology; Nicotine; Radiology; Positron-Emission Tomography; Neuroimaging; alpha7 Nicotinic Acetylcholine Receptor; Diseases; Chemicals and Drugs; Psychiatry and Psychology
Psychiatry: Center for Nicotine and Tobacco Use Research at Yale (CENTURY) | Cosgrove Lab | Translational Brain Imaging Program | VA Alcohol Research Center | Women's Behavioral Health Research, Division of | Yale Translational Center to Develop Gender-Sensitive Treatment for Tobacco Dependence
We are using novel, creative PET paradigms to gain insight into the neurochemical mechanisms that drive addiction and psychiatric disorders. PET allows us to measure specific molecules in the living human brain. We are particularly interested in identifying deficits in the cholinergic and dopaminergic neurotransmitter systems in tobacco smokers and how these systems change during acute and prolonged abstinence from smoking. We are uncovering the variables, such as sex, neurocognitive function, psychiatric status and genetic makeup that influence these changes. We are also examining the neuroadaptations that occur during the recovery from alcohol dependence including changes in the GABA-ergic system, the neuroimmune system, and synaptic plasticity.
Specialized Terms: Positron Emission Tomography; Neuroimaging; Alcohol Dependence; Tobacco Smoking; Nicotine Dependence; Brain; nicotinic acetylcholine receptor; GABAA-benzodiazepine receptor; Sex differences, Dopamine
Extensive Research Description
- Understanding the functional basis and behavioral and cognitive correlates of the changes in beta2*-nicotinic acetylcholine receptor availability during acute and prolonged abstinence in tobacco smokers.
- Examining the changes in GABAA-benzodiazepine receptor availability that occur during acute and prolonged abstinence from alcohol and nicotine dependence.
- Radiotracer development targeted at the glucocorticoid system.
- Examination of sex differences in the dopaminergic signature of smoking- and nicotine-induced dopamine release using novel PET brain imaging techniques.
- Understanding the role sex and hormonal status plays in brain changes in tobacco smokers.
- Examining the stress and neuroimmune system with PET and the application to psychiatric disorders such as PTSD.
- Cosgrove, K.P., Batis, J., Bois, F., Esterlis, I., Kloczynski, T., Stiklus, S., Maciejewski, P.K., Krishnan-Sarin, S., O’Malley, S., Perry, E., Tamagnan, G., Seibyl, J., and Staley, J.K. (2009) ß2-nicotinic acetylcholine receptor availability during acute and prolonged abstinence from tobacco smoking. Archives of General Psychiatry, 66, 666-676.
- Cosgrove, K.P., Mazure, C.M., and Staley, J.K. (2007). Evolving knowledge of sex differences in brain structure, function and chemistry. Biological Psychiatry, 62, 847-855.
- Staley, J.K., Krishnan-Sarin, S., Cosgrove, K.P., Krantzler, E., Frohlich, E., Perry, E., Dubin, J., Brenner, E., Baldwin, R.M., Tamagnan, G., Seibyl, J.P., Picciotto, M.R., London, E.D., O’Malley, S. and van Dyck, C.H. (2006). ß2*nicotinic acetylcholine receptor availability in recently abstinent smokers. Journal of Neuroscience, 26, 8707-8714.
- Cosgrove, KP, McKay, R, Esterlis, I, Kloczynski, T, Perkins, E, Bois, F, Pittman, B, Lancaster, J, Glahn, DC, O'Malley, SS, Carson, RE, and Krystal, JH (2014). Tobacco smoking interferes with GABAA receptor neuroadaptations during prolonged alcohol withdrawal, PNAS, 111, 18031-6.
- Gallezot, JD, Kloczynski, T, Weinzimmer, D, Labaree, D, Zheng, MQ, Lim, K, Rabiner, EA, Ridler, K, Pittman, B, Huang, Y, Carson, RE, Morris, ED, Cosgrove, KP. (2013) Imaging nicotine- and amphetamine-induced dopamine release in rhesus monkeys with [11C]PHNO versus [11C]raclopride PET. Neuropsychopharmacology, 39, 866-874.
- Sandiego, CM, Gallezot, JD, Pittman, B, Lim, K, Lin, S, Matuskey, D, Lee, J, O’Connor, KC, Nabulsi, N, Huang, Y, Carson, RE, Hannestad, J, and Cosgrove, KP. (2015). Imaging robust microglial activation after lipopolysaccharide administration in humans with PET. PNAS, 112, 12468-73.
- Cosgrove, KP, Wang, S, Kim, S-J, McGovern, E, Nabulsi, N, Gao, H, Labaree, D, Tagare, H, Sullivan, J, and Morris, ED (2014). Sex-Differences in the Brain's Dopamine Signature of Cigarette Smoking. Journal of Neuroscience, 34(50):16851-5.
- Hannestad, J, Gallezot, JD, Schafbauer, T, Lim, KP, Kloczynski, T, Morris, ED, Carson, RE, Ding, Y-S, Cosgrove, KP. (2012) Endotoxin-Induced Systemic Inflammation Activates Microglia:[11C]PBR28 Positron Emission Tomography in Nonhuman Primates. NeuroImage, 63, 232-239.
- Cosgrove, KP, Esterlis, I, McKee, SA, Bois, F, Seibyl, JP, Mazure, CM, Krishnan-Sarin, S, Staley, JK, Picciotto, MR, and O’Malley, SS. (2012) Sex differences in availability of β2*-nicotinic acetylcholine receptors in recently abstinent tobacco smokers. Archives of General Psychiatry, 69, 418-427.