Intradorsal hippocampal microinjection of lithium reverses morphine-induced impairment of memory in mice: interactions with dopamine receptor mechanism(s)

In this study, the influence of lithium administration on morphine-induced memory impairment and possible interactions with dopamine receptor mechanism have been investigated. Considering that the dorsal hippocampus is involved in memory, lithium and dopamine agents were injected into the CA1 regions of this site (intra-CA1). For memory assessment, a one-trial step-down inhibitory avoidance task was used in adult male mice. The results showed that posttraining subcutaneous administration of morphine (5 mg/kg) decreased the step-down latency on the test day, and this effect was reversed by pretest administration of the drug, which may be a form of morphine state-dependent learning. Interestingly, pretest intra-CA1 microinjection of different doses of lithium (2 and 4 mu g/mouse) reversed memory impairment induced by posttraining morphine (5 mg/kg, subcutaneously). In contrast, pretest intra-CA1 administration of either 131 receptor antagonist SCH23390 (0.01-1 mu g/mouse) or D2 receptor antagonist sulpiride (5-10 mu g/mouse) inhibited the improvement of memory retrieval by lithium (4 mu g/mouse, intra-CA1). Single pretest administration of SCH23390 or sulpiride neither elicited any response, nor reversed morphine-induced amnesia. In conclusion, it can be suggested that the dorsal hippocampal dopaminergic system is involved in the improving response of lithium on morphine-induced amnesia. Behavioural Pharmacology 20:680-687 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.