In the present study, influence of cholinergic drugs on lithium-induced state-dependent learning has been investigated in adult male NMRI mice. A single-trial step-down inhibitory avoidance task was selected. The results showed that post-training and pre-test intraperitoneal (i.p.) administration of lithium (10 mg/kg) induced state-dependent learning. In addition, pre-test administration of an anticholinesterase, physostigmine (0.3 and 0.6 mg/kg, i.p.) and nicotinic acetylcholine receptor agonist, nicotine (0.1 and 0.5 mg/kg) could substitute for pre-test lithium. Pre-test co-administration of an ineffective dose of physostigmine (0.1 mg/kg) but not nicotine (0.01 mg/kg), with lower doses of lithium (2.5 and 5 mg/kg) potentiated the effect of the latter drug on step-down latency. Post-training administration of a nonselective antagonist of muscarinic acetylcholine receptors, atropine, decreased the step-down latency, but pre-test administration of the same dose of the drug and also lithium, could not reverse the decrease of step-down latency. On the other hand, pre-test atropine at higher doses (0.3 and 0.6 mg/kg) disrupted lithium-induced state-dependent learning. On the contrary, the decrease of step-down latency due to post-training administration of another nonselective muscarinic antagonist, scopolamine (1 mg/kg, i.p.) reversed by pre-test administration of not only the same dose of the drug, but also lithium (10 mg/kg). Interestingly, pre-test administration of scopolamine (1 mg/kg) also reversed the decrease of step-down latency induced by post-training lithium (10 mg/kg). In conclusion, cholinergic system(s) may be involved in the lithium-induced state-dependent learning and the involvement of muscarinic receptors is more possible than nicotinic ones.
