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 10min the cocaine dose was systematically decreased (0.75-0.003mg/kg/infusion cocaine). After reaching stability on this procedure, rats were randomly pretreated with 0, 0.3, 1, or 3mg/kg naltrexone once every 3days, followed by random pretreatments of 0, 0.3, 1, or 3mg/kg morphine once every 3days. 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.
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 10min the cocaine dose was systematically decreased (0.75-0.003mg/kg/infusion cocaine). After reaching stability on this procedure, rats were randomly pretreated with 0, 0.3, 1, or 3mg/kg naltrexone once every 3days, followed by random pretreatments of 0, 0.3, 1, or 3mg/kg morphine once every 3days. 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.
Authors: Raymond F Anton; Gabor Oroszi; Stephanie O'Malley; David Couper; Robert Swift; Helen Pettinati; David Goldman Journal: Arch Gen Psychiatry Date: 2008-02
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