Abstract
A major obstacle in treating opioid use disorder is the persistence of drug seeking or craving during periods of abstinence, which is believed to contribute to relapse. Dopamine transmission in the mesolimbic pathway is posited to contribute to opioid reinforcement, but the processes by which dopamine influences drug seeking have not been completely elucidated. To examine whether opioid seeking during abstinence is associated with alterations in dopamine transmission, female and male rats self-administered oxycodone under an intermittent access schedule of reinforcement. Following self-administration, rats underwent a forced abstinence period, and cue-induced seeking tests were conducted to assess oxycodone seeking. One day following the final seeking test, rats were sacrificed to perform ex vivo fast scan cyclic voltammetry and western blotting in the nucleus accumbens. Rats displayed reduced dopamine uptake rate on abstinence day 2 and abstinence day 15, compared to oxycodone-naïve rats. Further, on abstinence day 15, rats had reduced phosphorylation of the dopamine transporter. Additionally, local application of oxycodone to the nucleus accumbens reduced dopamine uptake in oxycodone-naïve rats and in rats during oxycodone abstinence, on abstinence day 2 and abstinence day 15. These observations suggest that abstinence from oxycodone results in dysfunctional dopamine transmission, which may contribute to sustained oxycodone seeking during abstinence.
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