assessment of the effect of sertaline on the specific binding of 123-i mzint in healthy subjects

Conditions: Depression

Summary: the overall purpose of this project is to evaluate the effect of sertraline administration on the binding of 123-i mzint in 10 healthy subjects. all study procedures will be conducted at the institute for neurodegenerative disorders (ind) and molecular neuroimaging (mni) in new haven, ct.

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.

Eligibility criteria:
inclusion criteria: * the subject is aged 18-70. * written informed consent is obtained. * the participant has no clinically significant clinical laboratory value and/or clinically significant unstable medical, neurological or psychiatric illness. * for females, non-child bearing potential or negative urine pregnancy test on day of \[123i\] mzint injection. * willingness to comply with the study protocol exclusion criteria: * the subject has a clinically significant clinical laboratory values abnormality, and/or medical or psychiatric illness. * the subject has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery). * the subject has evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other disorder or disease. * use of all prescription drugs or non-prescriptions drugs that may effect serotonin such as antidepressants including sertraline, fluoxetine, fluvoxamine, venlafaxine within 60 days of baseline imaging study. * the participant has a history of alcohol, narcotic, or any other drug abuse as defined by the diagnostic and statistical manual of the american psychiatric association, 4th edition (dsm iv) {american psychiatric association, 1994 #2} within the past 2 years. * pregnancy

Keywords: neurological dopamine