Psychopharmacology

, Volume 180, Issue 3, pp 408–413

Characterization of conditioned place preference to cocaine in congenic dopamine transporter knockout female mice

  • Ivan O. Medvedev
  • Raul R. Gainetdinov
  • Tatyana D. Sotnikova
  • Laura M. Bohn
  • Marc G. Caron
  • Linda A. Dykstra
Original Investigation

DOI: 10.1007/s00213-005-2173-y

Cite this article as:
Medvedev, I.O., Gainetdinov, R.R., Sotnikova, T.D. et al. Psychopharmacology (2005) 180: 408. doi:10.1007/s00213-005-2173-y

Abstract

Rationale

The dopamine transporter (DAT) is thought to play a major role in the rewarding effects of cocaine. Therefore, it is surprising that cocaine reveals conditioned effects in DAT knockout (DAT-KO) mice.

Objectives

To examine these findings further, we obtained complete dose–effect curves for DAT-KO and DAT wild-type (DAT-WT) mice in a cocaine conditioned place preference (CPP) procedure.

Methods

Congenic C57BL6 background female DAT-KO and DAT-WT mice were conditioned in a three-compartment place preference apparatus. Conditioning consisted of three 30-min sessions with cocaine (2.5, 5.0, 10.0, 20.0, or 40.0 mg/kg) and three 30-min sessions with saline. The distribution of time in each choice compartment was determined after each pair of conditioning sessions (one cocaine and one saline session).

Results

DAT-WT mice revealed CPP over a wide range of cocaine doses (5.0–40 mg/kg), whereas DAT-KO mice revealed CPP over a more restricted range of doses, with consistent CPP only occurring with 10 mg/kg of cocaine.

Conclusions

CPP for cocaine develops in both DAT-KO and DAT-WT mice; however, the dose range at which CPP develops is much more restricted in DAT-KO mice than in DAT-WT mice. These observations corroborate the significant role of DAT inhibition in cocaine’s conditioned effects.

Keywords

CocaineDopamineKnockout miceDopamine transporterConditioned place preferenceReward

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Ivan O. Medvedev
    • 1
  • Raul R. Gainetdinov
    • 1
  • Tatyana D. Sotnikova
    • 1
  • Laura M. Bohn
    • 2
  • Marc G. Caron
    • 1
  • Linda A. Dykstra
    • 3
  1. 1.Department of Cell BiologyDuke University Medical CenterDurhamUSA
  2. 2.Department of PharmacologyThe Ohio State University College of Medicine and Public HealthColumbusUSA
  3. 3.Department of PsychologyUniversity of North Carolina at Chapel HillChapel HillUSA