Rationale: Serotonergic (5-HT) mechanisms appear to mediate central effects of cocaine. Therefore 5-HT disturbances could be associated with drug severity.
Objectives: We investigated whether prolactin (PRL) response to meta-chlorophenylpiperazine (m-CPP), a mixed 5-HT agonist/antagonist were associated with severity of cocaine use.
Methods: Thirty-six cocaine-dependent subjects and 33 controls underwent a challenge with 0.5 mg/kg of oral m-CPP. Severity of drug use was assessed using the Addiction Severity Index (ASI).
Results: The PRL response to m-CPP was significantly blunted in cocaine patients compared to controls (F = 21.86, p < 0.001). DeltaPRL (peak PRL-baseline PRL) was negatively correlated with ASI-drug (r = -0.45, p < 0.01), ASI-alcohol (r = -0.32, p < 0.05), and ASI-psychological (r = -0.41, p < 0.01) composite scores, and with the quantity, frequency and duration of drug use (r ranged from - 0.41 to - 0.32, p ranged from < 0.01 to 0.05). Hierarchical regressions showed that ASI-drug composite scores significantly predicted the variance in DeltaPRL after controlling for behavioral and demographic variables (F = 4.27, p < 0.05).
Conclusions: The results indicate that disturbances in 5-HT function as reflected by a blunted response to m-CPP seem to be primarily associated with severity of drug use and to a lesser, although significant extent with behavioral traits in cocaine-dependent patients.