Relationship of the serotonin transporter with prolactin response to meta-chlorophenylpiperazine in cocaine dependence.

BACKGROUND: Preclinical evidence indicates that exposure to cocaine influences the activity of the serotonin transporter (5-HTT) as well as several 5-HT receptor subtypes. However, little is known about the relationship between the 5-HTT and 5-HT receptors following cocaine exposure in humans. OBJECTIVE: We examined the relationship between platelet 5-HTT, a presynaptic 5-HT measure, and prolactin (PRL) response to meta-chlorophenylpiperazine (m-CPP), a postsynaptic 5-HT receptor agonist in cocaine dependent individuals. METHODS: Platelet [3H] paroxetine binding sites were assayed and the m-CPP challenge test was performed in 35 African American cocaine dependent individuals and 33 controls. Clinical measures included assessments of drug use severity and depression. RESULTS: Cocaine subjects showed reduced Bmax of [3H] paroxetine (t=4.67, p<0.01) and blunted PRL response to m-CPP (F=21.86, p<0.01) compared to controls. There was a positive correlation between Bmax and delta PRL [peak-baseline PRL] in cocaine subjects (r=0.50, p<0.01) but not in controls (r=0.19). ANCOVA analyses showed that the cocaine subgroup with moderate and severe reduction in Bmax showed a greater blunting in PRL response compared to the subgroup with mild Bmax reductions (F=9.44, p<.005). Multivariate regression models showed that the main effects as well as the interaction of Bmax and severity of cocaine use significantly contributed to impaired PRL response (F=17.90, p<.001). CONCLUSIONS: Disturbances in serotonin transporter binding and post-synaptic 5-HT receptor function seem to be associated in cocaine-dependent subjects. Severity of cocaine use appears to mediate this relationship. Whether there is a causal association between the two measures, or cocaine has separate and independent pre- and post-synaptic effects needs to be clarified.

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