Enriched Environment Ameliorates Cognitive Deficits and Locomotor Sensitization in Morphine-Withdrawn Rats Receiving Methadone Maintenance Treatment

Abstract

Objective: This study was designed to examine whether enriched environments (EE) would attenuate object recognition and spatial learning and memory deficits and locomotor sensitization induced by methadone maintenance treatment (MMT) in morphine-withdrawn rats. Methods: Male Wistar rats (170 ± 10 g) were injected with bi-daily doses (10 mg/kg, 12-h intervals) of morphine for 14 days. Rats receiving MMT were reared in the standard environment (SE) or EE during 30 days of morphine withdrawal. Then, the rats were tested for object recognition (the object recognition memory test, ORMT) and spatial learning and memory (the water maze) and then challenged with morphine (1 mg/kg, i.p.) and evaluated for locomotor activity (open-field box). Results: The results revealed that the dependent/saline/EE (D/Sal/EE) and D/methadone/EE (D/Meth/EE) rats exhibited significant preference for the new object (p = 0.006 and p = 0.049), spent more time in the target zone (p = 0.045 and p = 0.005) on the water maze, and displayed a lower level of distance traveled (p = 0.002 and p = 0.0001) compared to their control groups reared in SE. Conclusions: We conclude that exposure to EE could ameliorate the object recognition and spatial memory deficits and also decrease locomotor sensitivity in morphine-withdrawn rats receiving MMT. Thus, EE may be beneficial in the treatment of addiction during MMT.