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.