Rationale: In drug-dependent individuals, the primary excessive motivation is for drugs. Studies also indicate altered interest for "natural" rewarding activities associated with motivational disorders that may be relevant to drug dependence. However, to date, the impact of drug dependence and withdrawal upon motivation for "natural" rewards remains unclear.
Methods and objectives: In the present study, we use a food-driven operant behavior paradigm to assess the impact of opiate intake and withdrawal upon the motivational properties of highly palatable food (HPF) in mice.
Results: Our findings indicate that early (8-h) opiate withdrawal does not affect either the motivational or the discriminative properties of HPF intake. However, starting 32 h after the last morphine injection, opiate withdrawal increases operant behavior aimed at obtaining HPF. The increased HPF-driven behavior lasts at least 12 days following opiate withdrawal, indicating long-lasting effects upon motivation. Using a paradigm of reward contingency reversal, we also address the impact of opiate withdrawal upon cognitive functions. Our results indicate that opiate withdrawal does not affect the ability to learn a new operant rule to obtain HPF. Indeed, opiate withdrawal ameliorates the acquisition of the new HPF-driven operant task, most probably due to the persistent and long-lasting increased motivation. Finally, analysis of ambulatory activity and body weight (BW) changes reveal that motivational and cognitive effects are totally independent of caloric and/or motor effects of opiate dosing and withdrawal.
Conclusions: These results clearly demonstrate that excessive opiate intake and withdrawal produces dramatic and long-lasting motivational disorders relevant to drug dependence.