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

• Published in: Psychopharmacologia 2002-09, Vol.163 (2), p.238-248
• Main Authors: GILLISS, Brian, MALANGA, C. J, PIEPER, Jeanne O, CARLEZON, William A
• Format: Article
• Language: English
• Subjects: Addictions; Addictive behaviors; Animals; Behavior; Benzazepines - pharmacology; Biological and medical sciences; Brain - drug effects; Brain - physiology; Cocaine; Cocaine - pharmacology; Dopamine; Dose-Response Relationship, Drug; Drug addictions; Drug dosages; Drug Synergism; Drug withdrawal; Male; Medical sciences; Mice; Reaction Time - drug effects; Reaction Time - physiology; Reward; Signal transduction; Substance abuse treatment; Toxicology
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-002-1153-8

The dopamine D(1)-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. 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. 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. 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. 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.