Introduction: This study investigated the effect of the environmental enrichment during adolescence on morphine-induced Conditioned Place Preference (CPP) and locomotor sensitization in maternally separated male and female rat pups. Methods: Male Wistar rats were allowed to mate with female virgin Wistar rats. Pups were separated from them 3 hours per day during 2–14 days postnatal. All pups were weaned at 21 Postnatal Day (PND) and reared in standard environment or enriched environment from 21 to 50 PND with litter-mates of the same sex. The CPP and behavioral sensitization to morphine were assessed by an unbiased place conditioning paradigm and open filed method. Results: The results showed that the maternal separation enhanced morphine-induced CPP in both sexes, locomotor sensitization in male pups and tolerance to morphine-induced motor activity in female pups during adolescence. While, male and female pups reared in an EE exhibited a decrease in morphine-induced CPP, locomotor sensitization and tolerance induced by maternal separation compared to their control pups. Conclusion: Access to enriched environment during adolescence may have a protective effect against morphine-induced reward, locomotor sensitization and tolerance in adolescent male and female rats following maternal separation.

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