Concomitant abuse of methadone and methamphetamine could impair spatial learning and memory in male rats

Methadone maintenance therapy (MMT) has been considered as an effective medication for opioid dependence. However there are reports of methamphetamine abuse among MMT patients due to greater desired effects and fewer side effects than either substance alone. Little research has been done on the effects of methamphetamine abuse on cognitive behaviors during MMT. In the current study, we investigated spatial learning and memory along with the brain derived neurotrophic factor (BDNF) as important factors in neural plasticity under concomitant use of methadone and methamphetamine in male rats. The animals received administration of methadone (2.5 mg/Kg, SC, twice a day) and methamphetamine (0.5 mg/Kg, SC, once a day) concomitantly or either alone for 21 days. Three hours after each treatment, the rats were trained in eight-arm radial maze for 7 days, and their learning and working memory were evaluated. Moreover, western blotting was performed to evaluate hippocampal BDNF protein levels. The results showed that administration of methadone and methamphetamine concomitantly impaired spatial learning and memory more than methadone alone (P < 0.05). Additional western blotting analysis revealed that BDNF protein levels of hippocampus in the control group was more than the methadone group, while it was less than methamphetamine treated animals (P < 0.05). Our findings suggest that exposure to methamphetamine during methadone maintenance therapy could lead to spatial learning and memory impairments more than mere methadone.