Effects of treadmill exercise on methadone withdrawal-induced locomotor sensitization and the ventral pallidum and ventral tegmental area BDNF levels in morphine withdrawn rats receiving methadone maintenance treatment

This study examined the effects of treadmill exercise on the methadone withdrawal -induced locomotor sensitization, the ventral tegmental area (VTA) and ventral pallidum (VP) BDNF levels in morphine withdrawn rats receiving methadone maintenance treatment (MMT). The rats were chronically treated with bi-daily doses (10 mg/kg, at 12 h intervals) of morphine for 14 days. The exercising rats receiving MMT were forced to run on a motorized treadmill for 30 days during morphine withdrawal. Then, rats were exposed to a 14-day methadone withdrawal period, without any exercise and then challenged with morphine (1 mg/kg, ip) and evaluated for locomotor activity. Also, the VTA-VP BDNF levels were assessed before and after receiving MMT. The sedentary morphine-dependent rats receiving MMT and morphine-dependent rats receiving saline challenged to morphine exhibited a higher level of locomotor activity compared to Sal/Sal/Sed group after withdrawal of drug. While, the level of locomotor activity was lower in the D/Meth/Sed than in D/Sal/Sed rats. The VP BDNF level and the locomotors response were higher and lower, respectively in the D/Meth/Sed and D/Sal/Exc than the D/Sal/Sed rats. Exercise had no effect on the locomotors response and the VP BDNF levels in morphine-dependent rats receiving MMT. Our results showed that the sedentary morphine-dependent rats challenged to morphine enhanced the morphine-induced hyperlocomotion, whereas decreased the VP BDNF levels. MMT resulted in a persistent of locomotor sensitization caused by morphine withdrawal, though milder. Exercise had no effect on the locomotors response and the VTA-VP BDNF levels in the D/Meth/Exc.