Previous research by our group using [123I]beta-CIT SPECT has shown increased (approximately 25%) levels of dopamine transporters (DAT) in acutely abstinent (equal to or < 96 h) cocaine addicts as compared to healthy controls which persist 2-4 weeks after cessation of cocaine use. Recent findings from a separate cohort of formerly cocaine-dependent subjects (n=13) in residential drug treatment at Daytop (mean +/- 5D duration of treatment = 7.8 +/- 4.4 months; range 3-15 months) reveal an apparent return of [123I]beta-CIT binding to control levels. Either of two hypotheses may account for these results: 1) chronic cocaine exposure results in DAT elevations which """"""""normalize"""""""" with long-term (i.e., 8-month) abstinence/treatment, or 2) lower DAT levels have positive prognostic significance with respect to abstinence and retention in long-term (i.e., residential) drug treatment. The primary goal of the current proposal is to more definitively resolve these two alternative hypotheses by a """"""""within-subject"""""""" study Of cocaine-dependent subjects before and after residential drug treatment at Daytop. In addition, we propose to expand our assessments of Daytop subjects to include additional measures of synaptic DA function which are likely to be influenced by abstinence and/or drug treatment.
Three specific aims are proposed:
Aim#1 : To assess DAT levels in cocaine-dependent subjects before and after a 1-year period of residential drug treatment at Daytop using [123I]beta-CIT SPECT.
Aim#2 : To assess striatal and extrastriatal dopamine D2 receptors in cocaine-dependent subjects before and after a 1-year period of residential drug treatment at Daytop by [123I]epidepride SPECT.
Aim#3 : To assess basal levels of extracellular dopamine (DA) in cocaine-dependent subjects before and after a I-year period of residential drug treatment at Daytop by [123I]IBZM SPECT and a dopamine depletion paradigm employing the tyrosine hydroxylase inhibitor, alpha-methyl-para-tyrosine (AMPT). A total of 75(pre-treatment; 25 post-treatment) Daytop subjects and 25 healthy controls will participate in each of the SPECT imaging procedures above. These combined assessments will provide measures of pre-, post-, and intrasynaptic DA function, thereby establishing that 1) the effects of residential drug treatment on normalizing brain chemistry, or 2) the negative prognostic significance of abnormal brain DA function on treatment outcome for substance abuse.
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