Background: Lithium is used in treatment of bipolar disorders. Patients have shown learning and memory deficits due to lithium treatment. Interactions between lithium and opioids have been shown in some studies, but interaction of lithium and morphine on learning and memory has not been fully elucidated. In the present study, effects of i.c.v. injection of morphine on lithium state dependency has been investigated. Methods: An inhibitory avoidance task (step-down model) was used to assess memory in male NMRI mice. Results: Intraperitoneal (i.p.) injection of lithium (10 mg/kg) after training impaired memory on the test day, which was reversed by pre-test injection of the same dose of the drug. This is known as state-dependency. Pre-test injection of lithium (2 and 4 µg/mouse, i.c.v.) and morphine (3 and 6µg/mouse, i.c.v.) reversed memory impairment induced by post-training lithium (10mg/kg). Pre-test administration of naloxone (1 and 2 mg/kg, i.p.) prevented the effects of both morphine (3 μg/mouse, i.c.v.) and lithium (2 µg/mouse, i.c.v.) on memory retrieval. Conclusions: The results indicate a similar effect for lithium and morphine on reversal of lithium state-dependency. Therefore, it can be concluded that the effect of lithium on learning mediated through opioid receptors.
