A behavioral economic analysis of the effects of rimcazole on reinforcing effects of cocaine injection and food presentation in rats
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Rationale and objectives
Rimcazole, a σ-receptor antagonist with affinity for the dopamine transporter (DAT), decreases rates of cocaine self-administration at doses lower than those that affect food-reinforced responding. As response rates are multiply determined, behavioral-economic analyses were used to provide measures of the reinforcing effectiveness of cocaine and food after rimcazole treatment. Further, effects of combinations of the DAT inhibitor, methylphenidate, and σ-receptor antagonists (BD1008, BD1063) were compared to those of rimcazole to assess mechanism of rimcazole effects.
Male Sprague-Dawley rats were trained to lever press with food reinforcement (one or three 20-mg sucrose pellets) or cocaine injection (0.1 or 0.32 mg/kg) under fixed-ratio (FR) 5-response schedules. Drugs or vehicle were administered (i.p.) 5-min before sessions in which FR value was increased from 5 to 80. Economic demand functions were generated from effects of FR value (price) on intake (consumption), with the parameters of demand, consumption at no cost (Q0) and sensitivity to price (essential value, EV), derived.
Rimcazole dose-dependently decreased Q0 and EV at both cocaine doses/injection. In contrast, rimcazole had no effect on these parameters at either food amount. Combinations of methylphenidate and the σ-receptor antagonists decreased Q0 at the lower cocaine dose/injection but had no effect on EV; these treatments were ineffective on both economic parameters at the higher cocaine dose/injection and at either food amount.
Though the drug combinations only replicated rimcazole’s effects incompletely, the present results suggest a specific decrease in the reinforcing effects of cocaine due to dual DAT σ-receptor blockade.
KeywordsCocaine Rimcazole Sigma receptors Dopamine transporter Behavioral economics Self-administration
We thank Claudio Zanettini for expert advice in the conduct of the experiment, its analysis, and comments on the manuscript. We also thank Jean Lud Cadet for support, Maryann Carrigan for administrative assistance, and Amy H. Newman for supplies of rimcazole. The second author thanks Drs. James H. Woods and James E. Barrett for sustained encouragement, and the National Institute on Drug Abuse (NIDA) Intramural Research Program (IRP) for years of funding.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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