Single photon emission computed tomography, SPECT, allows for the measurement of the 3-D distribution of radioactive tracers in brain. Tracers in use fall into two main classes. In the first class, the tracer is taken up in brain in proportion to blood flow and thus can be utilized as a marker of neural activity. The second class of tracers binds to neurotransmitter receptors in brain such that the activity then reflects the distribution of the related neurochemistry. While previous work with cerebral blood flow agents was largely successful, other more sensitive means now exist for CBF measurements. Therefore, SPECT imaging has become our procedure of choice for in vivo neurochemistry. In clinical populations, we have performed studies with three radioligands. These include the dopamine D2 antagonist IBZM, the dopamine and serotonin transporter antagonist beta-CIT, and the muscarinic antagonist QNB. We have used these radioligands to examine clinical correlates of neurochemical function in drug-free schizophrenic patients, and to further elucidate the mechanism of action of neuroleptic drugs. We have also completed studies of dopaminergic and serotonergic function in patients with Tourettes syndrome and alcohol dependence. In non-human primate studies with these ligands we have testedneurochemical function in models of human neuropsychiatric illness. We have also conducted non-human primate studies to develop new radioligands. These include TISCH, a dopamine D1 receptor antagonist, and DOI, a serotonin 5HT2 agonist. - SPECT, IBZM, IQNB, BCIT, in vivo neurochemistry, dopamine, muscarinic receptors, schizophrenia - Human Subjects

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002660-07
Application #
6290560
Study Section
Special Emphasis Panel (CBDB)
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
1999
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Lu, Po H; Lee, Grace J; Raven, Erika P et al. (2011) Age-related slowing in cognitive processing speed is associated with myelin integrity in a very healthy elderly sample. J Clin Exp Neuropsychol 33:1059-68
Heinz, A; Jones, D W; Bissette, G et al. (2002) Relationship between cortisol and serotonin metabolites and transporters in alcoholism [correction of alcolholism]. Pharmacopsychiatry 35:127-34
Heinz, A; Mann, K; Weinberger, D R et al. (2001) Serotonergic dysfunction, negative mood states, and response to alcohol. Alcohol Clin Exp Res 25:487-95
Raedler, T J; Knable, M B; Jones, D W et al. (2000) In vivo olanzapine occupancy of muscarinic acetylcholine receptors in patients with schizophrenia. Neuropsychopharmacology 23:56-68
Heinz, A; Jones, D W; Raedler, T et al. (2000) Neuropharmacological studies with SPECT in neuropsychiatric disorders. Nucl Med Biol 27:677-82