title: Relationship of disinhibition and aggression to blunted prolactin response to meta-chlorophenylpiperazine in cocaine-dependent patients.
abstract: 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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC 27704, USA. Ashwin.Patkar@duke.edu
authors.forename: Ashwin A
authors.initials: AA
authors.lastname: Patkar
authors.forename: Paolo
authors.initials: P
authors.lastname: Mannelli
authors.forename: Kathleen
authors.initials: K
authors.lastname: Peindl
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Hill
authors.forename: Raman
authors.initials: R
authors.lastname: Gopalakrishnan
authors.forename: Wade H
authors.initials: WH
authors.lastname: Berrettini
mesh_terms: 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*
chemical_list: D010879:Piperazines; D017366:Serotonin Receptor Agonists; D011388:Prolactin; C015068:1-(3-chlorophenyl)piperazine