Rearing environment differentially modulates cocaine self-administration after opioid pretreatment: A behavioral economic analysis

Background Research has shown that previous experiences during development, especially if stressful, can alter an organism's response to opioids later in life. Given the previous literature on opioid modulation of cocaine self-administration, the current study raised rats in either an enriched condition (EC) or isolated condition (IC) and employed behavioral economics to study the effects of naltrexone and morphine on cocaine self-administration. Methods EC and IC rats were trained to lever press for cocaine using a within-session demand procedure. This procedure measured cocaine consumption under changing cocaine price by decreasing the dose of cocaine earned throughout a session. Rats were able to self-administer cocaine on a FR1; every 10 min the cocaine dose was systematically decreased (0.75–0.003 mg/kg/infusion cocaine). After reaching stability on this procedure, rats were randomly pretreated with 0, 0.3, 1, or 3 mg/kg naltrexone once every 3 days, followed by random pretreatments of 0, 0.3, 1, or 3 mg/kg morphine once every 3 days. Economic demand functions were fit to each rat's cocaine consumption from each pretreatment, and appropriate mathematical parameters were extracted and analyzed. Results Naltrexone decreased the essential value of cocaine in IC rats only. However, morphine decreased the essential value of cocaine and the consumption of cocaine at zero price in both EC and IC rats. Conclusion These results indicate that environmental experiences during development should be considered when determining the efficacy of opioid drugs, especially for the treatment of substance abuse.