biostudies-literatureKallupi MNIDA NIH HHSHHS | NIH | National Institute on Drug Abuse2140-2148https://www.ebi.ac.uk/biostudies/studies/S-EPMC6994987biostudies-literatureUnknown117(4)Approximately 25% of patients who are prescribed opioids for chronic pain misuse them, and 5 to 10% develop an opioid use disorder. Although the neurobiological target of opioids is well known, the molecular mechanisms that are responsible for the development of addiction-like behaviors in some but not all individuals are poorly known. To address this issue, we used a unique outbred rat population (heterogeneous stock) that better models the behavioral and genetic diversity that is found in humans. We characterized individual differences in addiction-like behaviors using an addiction index that incorporates the key criteria of opioid use disorder: escalated intake, highly motivated responding, and hyperalgesia. Using in vitro electrophysiological recordings in the central nucleus of the amProceedings of the National Academy of Sciences of the United States of AmericaNociceptin attenuates the escalation of oxycodone self-administration by normalizing CeA-GABA transmission in highly addicted rats.PMC6994987P50 DA037844U01 DA043799DA043799U01 DA044451DA044451Solberg Woods LCKallupi MKononoff JGeorge OPalmer AACarrette LLGSchweitzer Pde Guglielmo GfalseNociceptin attenuates the escalation of oxycodone self-administration by normalizing CeA-GABA transmission in highly addicted rats.Approximately 25% of patients who are prescribed opioids for chronic pain misuse them, and 5 to 10% develop an opioid use disorder. Although the neurobiological target of opioids is well known, the molecular mechanisms that are responsible for the development of addiction-like behaviors in some but not all individuals are poorly known. To address this issue, we used a unique outbred rat population (heterogeneous stock) that better models the behavioral and genetic diversity that is found in humans. We characterized individual differences in addiction-like behaviors using an addiction index that incorporates the key criteria of opioid use disorder: escalated intake, highly motivated responding, and hyperalgesia. Using in vitro electrophysiological recordings in the central nucleus of the am2020-01-01T00:00:00Z2020 Jan2025-04-04T14:59:29.355Z2025-04-04T14:59:29.355ZS-EPMC69949873193245010.1073/pnas.1915143117