Study of the effects of controlled morphine administration for treatment of anxiety, depression and cognition impairment in morphine-addicted rats.

Background: Morphine dependency usually results in undesired outcomes such as anxiety, depression, and cognitive alterations. In this study, morphine was used to manage morphine dependence-induced anxiety, depression, and learning and memory disturbances.

Materials And Methods: Forty rats were divided equally into five groups. Group 1 received saline for 21 days. Groups 2-5 were dependent by increasing administration of morphine (15-45 mg/kg) for 7 days. For the next 14 days, morphine was administered as the following regimen: Group 2: once daily; 45 mg/kg (positive controls), Group 3: the same dose with an increasing interval (6 h longer than the previous intervals each time), Group 4: the same dose with an irregular intervals (12, 24, 36 h intervals interchangeably), and Group 5: decreasing doses once daily (every time 2.5 mg/kg less than the former dosage). On days 22-26, elevated plus maze (EPM), open field test (OFT), forced swim test (FST), and tail suspension test (TST) were performed to investigate anxiety level and depression in animals. Between 17 and 21 days, Morris water maze (MWM) was used to evaluate the spatial learning and memory.

Results: Chronic morphine administration caused depression and anxiety as observed by FST, EPM, and TST and decreased motor activity in OFT and caused impairment in learning and memory performance in MWM. Treatment with our protocol as increasing interval, irregular interval, and decreasing dosage of morphine caused marked reduction in depression, anxiety, and improved cognition performance compared with positive control group; and attenuated motor deficits in morphine-dependent rats, remarkably.

Conclusions: Change in dosage regimens of morphine can reduce morphine-induced anxiety, depression, and cognitive impairments.