The dopaminergic system plays a role in the effect of lithium on inhibitory avoidance memory in mice

Abstract

The effects of dopaminergic drugs on the inhibitory avoidance memory affected by lithium were examined in the Naval Medical Research Institute (NMRI) mice using a single-trial step-down inhibitory (passive) avoidance task. The results showed that post-training administration of lithium (10 mg/kg, i.p.) decreased the step-down latency on the test day, which was fully or partly reversed by pre-test administration of the same dose of the drug; suggesting state-dependent learning induced by lithium. Our results also showed that pre-test (i.p.) administration of the dopamine D1 receptor agonist SKF38393 and the dopamine D2 receptor agonist quinpirole by themselves and in combination with ineffective doses of lithium (0.3, 0.6 and 1.25 mg/kg) reversed the decrease of the step-down latency induced by post-training lithium. In contrast, pre-test administration of the dopamine D1 receptor antagonist SCH23390 (0.025, 0.05 and 0.1 mg/kg, i.p.) and the dopamine D2 receptor antagonist sulpiride (6.25 and 12.5 mg/kg, i.p.) alone or in combination with pre-test lithium (10 mg/kg), did not significantly alter the step-down latency on the test day, except for a higher dose of sulpiride (25 mg/kg) which by itself increased the step-down latency. Furthermore, pre-test administration of a lower dose of sulpiride (3 mg/kg) in combination with ineffective doses of lithium (03, 0.6 and 1.25 mg/kg) also reversed the decrease in the step-down latency induced by post-training lithium. In conclusion, the dopamine D1 and D2 receptor mechanism(s) may be involved, at least partly, in the effect of lithium on retrieval of the inhibitory avoidance memory influenced by the drug.