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

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.