Role of ventral subiculum in incubation of oxycodone craving after electric barrier-induced voluntary abstinence

In humans, abstinence is often self-imposed, and relapse typically involves a conflict situation where addicts choose between the desire to experience the drug’s rewarding effects and adverse consequences of drug seeking. To mimic this human condition, we recently developed a rat model of incubation of oxycodone craving after electric barrier-induced voluntary abstinence and showed time-dependent increases in drug seeking on abstinence day 15 and 30 compared to day 1 (incubation of oxycodone craving) that was more pronounced than the classical incubation of craving after homecage forced abstinence. Here, we examined the role of ventral subiculum (vSub) in incubation of oxycodone seeking after electric barrier-induced abstinence, using the activity marker Fos and muscimol + baclofen (GABA A+B receptor agonists) inactivation. We trained male and female rats to self-administer oxycodone (0.1 mg/kg/infusion, 6-h/d) for 14 days. We then introduced an electric barrier near the drug-paired lever of increasing intensity (0.1 to 0.4 mA) that causes cessation of oxycodone self-administration. Next, we tested the rats (n=6-7/group) for relapse to oxycodone seeking (extinction tests) in the absence of shock and drug on abstinence day 15 and extracted the brains for Fos-immunohistochemistry or tested the rats (n=10-12/group) after vSub injections of vehicle or muscimol + baclofen. Relapse after electric barrier-induced abstinence was associated with increased Fos expression in vSub and local inactivation of vSub decreased “incubated” oxycodone seeking. Together, these data demonstrate a role of vSub in incubation of oxycodone craving after cessation of drug taking due to adverse consequences of drug seeking.