Assessment of the Effect of Sertaline on the Specific Binding of 123-I MZINT in Healthy Subjects

Serotonin (5-HT) is a monoamine neurotransmitter found in the peripheral and central nervous system. It is responsible for regulating a wide variety of physiological processes and higher CNS functions. 5-HT neurons project diffusely throughout the brain, innervating the cerebral cortex, hippocampus, thalamus, midbrain, brainstem and cerebellum, and play a prominent role in regulating physiological and behavioral responses such as arousal, thermoregulation, anxiety, and affect. All subjects will undergo written informed consent and a screening evaluation including baseline clinical laboratory testing, and a baseline physical and neurological evaluation. healthy subjects will undergo a baseline 123-I MZINT injection and SPECT imaging described below. At baseline, healthy subjects will be started on either no treatment (n=4), or one of three different doses of sertraline (25 mg/day n=2, 50 mg/day n=2 or 150 mg/day n=2), which will be administered over a 14 day period. Fourteen days following imaging session 1, all subjects (treated with sertraline and untreated) will undergo a second 123-I MZINT and SPECT imaging study. Data from the baseline and follow-up SPECT images will be compared to evaluate for any effect of sertraline on regional brain uptake of 123-I MZINT. The subjects that are randomized to no treatment will serve as controls and provide preliminary test-retest reproducibility data on the imaging outcome measure. The goal of this proposal is to evaluate the effect of sertraline administration on the specific \[123-I\] mZINT. In vitro and in vivo data from early human studies and baboon studies strongly support further evaluation of \[123I\] mZINT in healthy subjects.