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Intermittent access to oxycodone decreases dopamine uptake in the nucleus accumbens core during abstinence
Journal article   Open access   Peer reviewed

Intermittent access to oxycodone decreases dopamine uptake in the nucleus accumbens core during abstinence

Kyle R. Samson, Wei Xu, Sandhya Kortagere and Rodrigo A. España
Addiction biology, v 27(6), pp e13241-n/a
Nov 2022
PMID: 36301217
url
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10262085View
Accepted (AM)Open Access (License Unspecified) Open

Abstract

craving dopamine transporter dopamine uptake opioid self‐administration threonine 53
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. Intermittent access to oxycodone reduced dopamine uptake rate in the nucleus accumbens core on abstinence days 2 and 15. Additionally, acute application of oxycodone to the nucleus accumbens core induced a robust reduction in dopamine uptake.

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Web of Science research areas
Biochemistry & Molecular Biology
Substance Abuse
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