Role of orbitofrontal cortex in incubation of oxycodone craving in male rats
Autor: | Kristine T. Garcia, Rachel D. Altshuler, Eddy S. Yang, Ian R. Davis, Xuan Li, Adedayo Olaniran, Meron Haile, Syrus Razavi |
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Rok vydání: | 2020 |
Předmět: |
Male
medicine.medical_specialty Drug-Seeking Behavior Prefrontal Cortex Medicine (miscellaneous) Craving behavioral disciplines and activities Heroin Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Internal medicine mental disorders medicine Animals Premovement neuronal activity Incubation Pharmacology business.industry Genes fos Rats 030227 psychiatry Psychiatry and Mental health Endocrinology Opioid behavior and behavior mechanisms Orbitofrontal cortex medicine.symptom Self-administration business Oxycodone psychological phenomena and processes 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Addiction Biology. 26 |
ISSN: | 1369-1600 1355-6215 |
DOI: | 10.1111/adb.12927 |
Popis: | One of the main challenges in treating opioid-use disorders is relapse during abstinence, triggered by re-exposure to drug-associated cues. Previous studies have demonstrated that drug-seeking in rats progressively increases over time during withdrawal (incubation of drug craving). Here, we used male rats and examined neural mechanisms underlying incubation of craving to oxycodone, a commonly abused prescription opioid, and we focused on orbitofrontal cortex (OFC), a brain region previously implicated in incubation of heroin craving. We first used neuronal activity marker Fos and measured neuronal activation in OFC (ventral and lateral OFC) associated with day-1 and day-15 relapse tests. Next, we determined the effect of pharmacological reversible inactivation of OFC on incubated oxycodone seeking on withdrawal day 15. Finally, we determined the effect of reversible inactivation of OFC on nonincubated oxycodone seeking on withdrawal day 1. We found that lever presses during relapse tests were higher on withdrawal day 15 than on withdrawal day 1 (incubation of oxycodone craving). Incubation of oxycodone craving is accompanied with a time-dependent increase of Fos protein expression in both ventral and lateral OFC. Lastly, OFC inactivation decreased oxycodone seeking on withdrawal day 15 but had no effect on withdrawal day 1. Together with the previous heroin study, results here show that OFC plays a critical role in incubation of opioid craving. |
Databáze: | OpenAIRE |
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