Psychopharmacology

, Volume 185, Issue 1, pp 123–132 | Cite as

Relationship of disinhibition and aggression to blunted prolactin response to meta-chlorophenylpiperazine in cocaine-dependent patients

  • Ashwin A. Patkar
  • Paolo Mannelli
  • Kathleen Peindl
  • Kevin P. Hill
  • Raman Gopalakrishnan
  • Wade H. Berrettini
Original Investigation
First Online:
Received:
Accepted:

Abstract

Rationale

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 ΔPRL (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 ΔPRL in cocaine patients.

Conclusion

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.

Keywords

Serotonin m-CPP 5-HT Cocaine Substance abuse 
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Notes

Acknowledgements

This research was supported in part by grants DA00340 and DA015504 to A.A.P. from the National Institute on Drug Abuse. The authors thank Edward Gottheil, M.D., Ph.D., for facilitating recruitment.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Ashwin A. Patkar
    • 1
  • Paolo Mannelli
    • 1
  • Kathleen Peindl
    • 1
  • Kevin P. Hill
    • 2
  • Raman Gopalakrishnan
    • 3
  • Wade H. Berrettini
    • 4
  1. 1.Department of Psychiatry and Behavioral SciencesDuke UniversityDurhamUSA
  2. 2.Department of MedicineYale UniversityNew HavenUSA
  3. 3.Department of PsychiatryThomas Jefferson UniversityPhiladelphiaUSA
  4. 4.Center for Neurobiology and Behavior, Department of PsychiatryUniversity of PennsylvaniaPhiladelphiaUSA

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