Methadone is used as a
substitution drug for the treatment of
opioid dependence and
chronic pain. Despite its widespread use and availability, there is a serious concern with respect to the relative safety of
methadone. The purpose of this study was to characterize how acute
methadone overdose affects the cognitive and motor performance of naïve healthy rats. The
methadone overdose was induced by administering an acute toxic dose of
methadone (15 mg/kg; ip; the equivalent dose of 80% of LD50) to adolescent rats.
Resuscitation using a
ventilator pump along with a single dose of
naloxone (2 mg/kg; ip) was administered following the occurrence of
apnea. The animals which were successfully resuscitated divided randomly into three
apnea groups that evaluated either on day 1, 5, or 10 post-
resuscitation (M/N-Day 1, M/N-Day 5, and M/N-Day 10 groups) in the Y-maze and novel object memory recognition tasks as well as pole and rotarod tests. The data revealed that a single toxic dose of
methadone had an adverse effect on spontaneous behavior. In addition, Recognition memory impairment was observed in the M/N-Day 1, 5, and 10 groups after
methadone-induced
apnea. Further, descending time in the M/N-Day 5 group increased significantly in comparison with its respective Saline control group. The overall results indicate that acute
methadone-overdose-induced
apnea produced delay-dependent cognitive and motor impairment. We suggest that
methadone poisoning should be considered as a possible cause of delayed
neurological disorders, which might be transient, in some types of memory or motor performance in naïve healthy rats.