Project: Psychiatric Molecular Imaging Program (PMIP)

The PET facility houses the Psychiatric Molecular Imaging Program (PMIP). The mission of the PMIP is to use PET radiotracers to understand neurochemical abnormalities in addictive disorders in humans. PET investigations in the lab have traditionally focused on developing and validating novel imaging paradigms to measure neurochemical transmission in humans. For example, studies have used [11C]FLB 457 PET and amphetamine to measure cortical dopamine release in cocaine and alcohol use disorders (1, 2); and [11C]flumazenil and tiagabine to measure GABA release in psychotic disorders (3). The group's focus is to apply these novel imaging techniques to characterize neurochemical abnormalities in humans with addictive and stress disorders. Ongoing studies with [11C]NOP-1A PET seek to clarify the role of nociceptin, a resilience promoting neuropeptide transmitter in reward/reinforcement, and stress-induced relapse in addiction (4-6). Future studies in addiction plan to use a novel [11C]NOP-1A and hydrocortisone challenge paradigm (shown in Figure) to examine the interactions between corticotropin-releasing factor and nociceptin receptors (7). Other areas in which the group has an active interest are the role of omega-3 fatty acid status/supplementation on brain health; alcohol’s effects on cognitive decline in middle-aged adults; and the neurochemical abnormalities that promote stress and relapse in opioid use disorders. The group is also interested in pursuing novel radioligands to image other receptors such as orexin-1, neurokinin-1 and neuropeptide Y Y1 that modulate stress and lead to relapse in addiction.

    1. Narendran R, Mason NS, Himes ML, Frankle WG (2020): Imaging Cortical Dopamine Transmission in Cocaine Dependence: A [(11)C]FLB 457-Amphetamine Positron Emission Tomography Study. Biol Psychiatry.
    2. Narendran R, Mason NS, Paris J, Himes M, Douaihy AB, Frankle G (2014): Prefrontal cortical dopamine transmission is decreased in alcoholism. Am J Psychiatry. In press.
    3. Frankle WG, Cho RY, Prasad KM, Mason NS, Paris J, Himes ML, et al. (2015): In vivo measurement of GABA transmission in healthy subjects and schizophrenia patients. Am J Psychiatry. 172:1148-1159.
    4. Narendran R, Ciccocioppo R, Lopresti B, Paris J, Himes ML, Mason NS (2018): Nociceptin Receptors in Alcohol Use Disorders: A Positron Emission Tomography Study Using [(11)C]NOP-1A. Biol Psychiatry. 84:708-714.
    5. Narendran R, Tollefson S, Himes ML, Paris J, Lopresti B, Ciccocioppo R, et al. (2019): Nociceptin Receptors Upregulated in Cocaine Use Disorder: A Positron Emission Tomography Imaging Study Using [(11)C]NOP-1A. Am J Psychiatry. 176:468-476.
    6. Narendran R, Tollefson S, Fasenmyer K, Paris J, Himes ML, Lopresti B, et al. (2019): Decreased Nociceptin Receptors Are Related to Resilience and Recovery in College Women Who Have Experienced Sexual Violence: Therapeutic Implications for Posttraumatic Stress Disorder. Biol Psychiatry. 85:1056-1064.
    7. Flanigan M, Tollefson S, Himes ML, Jordan R, Roach K, Stoughton C, et al. (2020): Acute Elevations in Cortisol Increase the In Vivo Binding of [(11)C]NOP-1A to Nociceptin Receptors: A Novel Imaging Paradigm to Study the Interaction Between Stress- and Antistress-Regulating Neuropeptides. Biol Psychiatry. 87:570-576.