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. 2021 Mar;26(2):e12927.
doi: 10.1111/adb.12927. Epub 2020 Jun 22.

Role of orbitofrontal cortex in incubation of oxycodone craving in male rats

Rachel D Altshuler  1 , Eddy S Yang  1 , Kristine T Garcia  1 , Ian R Davis  1 , Adedayo Olaniran  1 , Meron Haile  1 , Syrus Razavi  1 , Xuan Li  1
Affiliations

Role of orbitofrontal cortex in incubation of oxycodone craving in male rats

Rachel D Altshuler et al. Addict Biol. 2021 Mar.

Abstract

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.

Keywords: Fos; incubation of craving; orbitofrontal cortex; oxycodone; relapse; self-administration.

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References

REFERENCES

    1. Kariisa M, Scholl L, Wilson N, Seth P, Hoots B. Drug overdose deaths involving cocaine and psychostimulants with abuse potential - United States, 2003-2017. MMWR Morb Mortal Wkly Rep. 2019;68(17):388-395.
    1. Gostin LO, Hodge JG Jr, Noe SA. Reframing the opioid epidemic as a national emergency. JAMA. 2017;318(16):1539-1540.
    1. Stuart GL, Shorey RC, France CR, et al. Empirical studies addressing the opioid epidemic: an urgent call for research. Subst Abuse. 2018;12:1178221818784294.1-4.
    1. O'Brien CP, Ehrman RN, Ternes JW. Classical conditioning in human opioid dependence. In: Goldberg S, Stolerman I, eds. Behavioral Analysis of Drug Dependence. Orlando: Academic Press; 1986:329-356.
    1. Neisewander JL, Baker DA, Fuchs RA, Tran-Nguyen LT, Palmer A, Marshall JF. Fos protein expression and cocaine-seeking behavior in rats after exposure to a cocaine self-administration environment. J Neurosci. 2000;20(2):798-805.

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