Cocaine and SKF-82958 potentiate brain stimulation reward in Swiss-Webster mice
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- Gilliss, B., Malanga, C., Pieper, J.O. et al. Psychopharmacology (2002) 163: 238. doi:10.1007/s00213-002-1153-8
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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.