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Assessment of the Specificity of the Effects of Rimcazole on the Reinforcing Effects of Cocaine Using a Behavioral Economic Approach
Author(s) -
Job Martin O.,
Katz Jonathan L.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.986.10
Subject(s) - antagonist , reinforcement , self administration , methylphenidate , psychology , pharmacology , chemistry , receptor , anesthesia , medicine , social psychology , psychiatry , attention deficit hyperactivity disorder
Previous research has shown that cocaine self‐administration is decreased by rimcazole, a sigma (σ) receptor antagonist that also binds to the dopamine transporter (DAT). However, it is uncertain if those decreases are due to an action of rimcazole on the reinforcing effect of cocaine. One way to assess reinforcing effects is with an analysis of demand curves that show the decreases in consumption of a reinforcer with increasing cost. From the demand curve, the fitted parameters for consumption at no cost (Q 0 ) and the essential value of the reinforcer (EV, a measure derived from the sensitivity to price) can be derived. Because rimcazole has actions at both the DAT and σ receptors, its effects were compared to that of combinations of a σ receptor antagonist (BD 1008) and a standard DAT inhibitor (methylphenidate). Rimcazole (3.2, 10 and 32 mg/kg) or vehicle were administered (i.p.) to male Sprague‐Dawley rats 5 minutes before sessions in which the number of lever presses required per infusion for either of two doses of cocaine (0.1 or 0.32 mg/kg/infusion) or food (three 20 mg pellets) were increased within sessions. The effects of combinations of methylphenidate (1 mg/kg i.p.) and different doses of BD 1008 (0, 3.2, 10 mg/kg) on the demand curve for cocaine (0.1 or 0.32 mg/kg/infusion) or food were determined under similar conditions. Demand curves were fitted to the data using an exponential model (Hursh and Silberberg, Psyc Rev 115: 186, 2008). Rimcazole dose‐dependently decreased both Q 0 and EV at doses that had no effect on food‐reinforced responding. The combination of methylphenidate and the highest dose of BD 1008 also decreased Q 0 , though only at the 0.1 mg/kg/infusion dose of cocaine. In contrast the combination had no effect on the behavioral economic parameters derived from food‐reinforced responding. The present results indicate that rimcazole specifically alters the reinforcing effects of cocaine, but not food. Further, the similarity in effects of the combinations of methylphenidate and BD 1008 to rimcazole suggests that dual inhibition of both the DAT and σ receptors shows specificity in decreasing the reinforcing effects of cocaine and may provide targets for discovery of a combination chemotherapy for cocaine abuse. Support or Funding Information This work was supported by NIDA/NIH.