Behavioral flexibility and response selection are impaired after limited exposure to oxycodone

Abstract

Behavioral flexibility allows individuals to adapt to situations in which rewards and goals change. Potentially addictive drugs may impair flexible decision-making by altering brain mechanisms that compute reward expectancies, thereby facilitating maladaptive drug use. To investigate this hypothesis, we tested the effects of oxycodone exposure on rats in two complementary learning and memory tasks that engage distinct learning strategies and neural circuits. Rats were trained first in either a spatial or a body-turn discrimination on a radial maze. After initial training, rats were given oxycodone or vehicle injections in their home cages for 5 d. Reversal learning was tested 36 h after the final drug exposure. We hypothesized that if oxycodone impaired behavioral flexibility, then drug-exposed rats should learn reversals more slowly than controls. Oxycodone exposure impaired spatial reversal learning when reward contingencies changed rapidly, but not when they changed slowly. During rapid reversals, oxycodone-exposed rats required more trials to reach criterion, made more perseverative errors, and were more likely to make errors after correct responses than controls. Oxycodone impaired body-turn reversal learning in similar patterns. Limited exposure to oxycodone reduced behavioral flexibility when rats were tested in a drug-free state, suggesting that impaired decision-making is an enduring consequence of oxycodone exposure.

Chronic alcohol drinking persistently suppresses thalamostriatal excitation of cholinergic neurons to impair cognitive flexibility

“…Alcohol use disorder is a chronic brain disorder characterized by an inability to stop drinking despite the resultant adverse consequences (1,2). This inability is associated with impaired flexibility in decision making, which contributes to compulsive alcohol use (1)(2)(3)(4)(5). Increasing evidence suggests that the dorsomedial striatum (DMS) is involved in cognitive flexibility (6)(7)(8)(9)(10)(11).…”

Opioid modulation of cognitive impairment in depression

“…Unstressed females receiving β-FNA also made fewer errors during reversal (Laredo et al, 2015). In a different form of a reversal learning task conducted on the radial arm maze, acute oxycodone impaired spatial reversal learning when reward rules were changed quickly, but not when they changed slowly (Seip-Cammack and Shapiro, 2014). Overall, these data indicate a role for MORs and KORs in the modulation of behavioral flexibility, but further research is required using more complex cortical dependent tasks.…”

Adult consequences of prenatal drug exposure

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“…These deficits are associated with functional abnormalities that may persist for years even after abstinence . Down‐regulation of neurotransmitter function is linked to neurocognitive impairment and dysfunction in both animals and humans and indeed, drug addiction is hypothesised to be the result of enduring changes to ventral striatal and prefrontal cortical circuits that receive input from midbrain dopaminergic neurons governing affective and cognitive functions . Babies who are exposed to intra‐uterine opioids have significantly smaller whole brain, basal ganglia and cerebellar volumes than other children but whether this is caused by drug exposure or other factors (e.g.…”