Altered motivation and learning following opiate withdrawal: evidence for prolonged dysregulation of reward processing.

Opiate abuse has been associated with cognitive deficits in human addicts. To determine if prior opiate exposure alters the ability to learn, we trained animals in an instrumental learning task for a food reward. During a 2-week period after withdrawal, morphine-abstinent rats were significantly slower at learning an escalating fixed-ratio response for food reward compared to placebo-treated animals. When these same animals were trained in a conditioned suppression paradigm (two tone-shock pairings given in the operant box), the morphine-withdrawn animals showed greater retention by taking significantly longer to resume responding for food reward when the tone was presented. In a third experiment, morphine-abstinent rats withdrawn 2 or 5 weeks were tested for their ability to associate a highly palatable food reward with a specific environment using a place-conditioning paradigm. At 2 weeks postwithdrawal, morphine-abstinent rats did not show any significant place preference for a food they readily consumed, while placebo-treated rats readily learned to prefer the food-paired environment. At 5 weeks postwithdrawal, rats developed significantly less preference for food-associated cues, but more preference for morphine-associated cues, compared to placebo-treated animals. These data suggest that prior morphine exposure may have prolonged effects on the motivation for natural rewards, which in turn may compromise the ability of former addicts to overcome their addictions.