Psychopharmacology

, Volume 163, Issue 2, pp 238–248

Cocaine and SKF-82958 potentiate brain stimulation reward in Swiss-Webster mice

  • Brian Gilliss
  •  C. Malanga
  • Jeanne O. Pieper
  • William A. Carlezon
Original Investigation

DOI: 10.1007/s00213-002-1153-8

Cite this article as:
Gilliss, B., Malanga, C., Pieper, J.O. et al. Psychopharmacology (2002) 163: 238. doi:10.1007/s00213-002-1153-8

Heading

Abstract

Rationale. The dopamine D1-like receptor agonist SKF-82958 reportedly blocks reinstatement of cocaine-seeking behavior in rats and non-human primates. It is not known if SKF-82958 reduces drug-seeking behaviors in animals exposed previously to cocaine by causing reward-like effects or withdrawal-like aversive effects.

Objectives. Intracranial self-stimulation (ICSS) studies were conducted to determine if SKF-82958 has reward-like or withdrawal-like effects in mice exposed previously to cocaine, or under the influence of cocaine at the time of testing.

Methods. Swiss-Webster mice with lateral hypothalamic stimulating electrodes were trained to self-administer rewarding brain stimulation. The mice were tested in a "curve-shift" variant of the ICSS procedure after intraperitoneal administration of cocaine alone (2.5–20 mg/kg), SKF-82958 alone (0.03–0.3 mg/kg), or a mixture of both drugs (SKF 0.03 mg/kg+2.5 or 5.0 mg/kg cocaine). Each treatment was given twice.

Results. Cocaine and SKF-82958 each caused dose-dependent decreases in brain stimulation reward thresholds that were largest immediately after administration. A dose of SKF-82958 with no reward-related effects of its own potentiated the reward-related effects of low doses of cocaine. Repeated administration did not cause progressive changes in the ability of any treatment to decrease thresholds.

Conclusions. Cocaine and SKF-82958 each potentiate the rewarding effects of lateral hypothalamic brain stimulation in Swiss-Webster mice, implying that these drugs have rewarding effects of their own. The reward-facilitating effects of low doses of cocaine and SKF-82958 are additive (or synergistic). These data suggest that SKF-82958 may decrease cocaine-seeking behavior by mechanisms related to reward rather than aversion.

Brain stimulation reward Intracranial self-stimulation Cocaine D1 agonist Addiction Mice

Copyright information

© Springer-Verlag 2002

Authors and Affiliations

  • Brian Gilliss
    • 1
  •  C. Malanga
    • 1
  • Jeanne O. Pieper
    • 2
  • William A. Carlezon
    • 1
  1. 1.Department of Psychiatry, Harvard Medical School and McLean Hospital, MRC 217, 115 Mill Street, Belmont, MA 02478, USA
  2. 2.Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA