Relationship of disinhibition and aggression to blunted prolactin response to meta-chlorophenylpiperazine in cocaine-dependent patients.
BACKGROUND
Considerable evidence indicates that serotonergic (5-HT) mechanisms may mediate central effects of cocaine, and disinhibition and aggression.


OBJECTIVE
We investigated whether prolactin (PRL) response to meta-chlorophenylpiperazine (m-CPP), a mixed 5-HT agonist/antagonist, differed between abstinent cocaine-dependent patients and controls and whether m-CPP challenge responses were related to measures of disinhibition and aggression.


METHODS
Thirty-five cocaine-dependent African-American subjects who were abstinent for at least 2 weeks and 33 African-American controls underwent assessments of disinhibition and aggression and a challenge with 0.5 mg/kg of oral m-CPP.


RESULTS
The PRL response to m-CPP was compared between cocaine patients and controls and between subgroups categorized high or low based on disinhibition and aggression measures. Hierarchical regressions were used to determine whether behavioral measures predicted deltaPRL (peak PRL-baseline PRL). The PRL response to m-CPP was significantly diminished in cocaine patients compared to controls. The blunting was more robust in cocaine patients with high disinhibition and aggression. Among cocaine patients, the high-disinhibition subgroup showed greater blunting than the low-disinhibition subgroup and there was a trend for the high-aggression subgroup to be more blunted than the low-aggression subgroup. The subgroups of controls did not differ from each other. A combination of disinhibition and aggression measures significantly predicted deltaPRL in cocaine patients.


CONCLUSIONS
The results indicate that cocaine-dependent patients show disturbances in postsynaptic 5-HT function during early abstinence. It appears that the 5-HT disturbances are more pronounced in the subgroup of cocaine patients with high disinhibition and aggression.
Patkar
Ashwin A
AA
Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC 27704, USA. Ashwin.Patkar@duke.edu
Mannelli
Paolo
P
Peindl
Kathleen
K
Hill
Kevin P
KP
Gopalakrishnan
Raman
R
Berrettini
Wade H
WH
D000328:Adult; D000374:Aggression / Q000187:drug effects; D001519:Behavior / Q000187:drug effects*; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007266:Inhibition, Psychological; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011388:Prolactin / Q000096:biosynthesis*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D010879:Piperazines; D017366:Serotonin Receptor Agonists; D011388:Prolactin; C015068:1-(3-chlorophenyl)piperazine