Effects of concurrent manipulations of nicotinic and muscarinic receptors on spatial and passive avoidance learning.

The present study investigates the effects of concurrent manipulations of nicotinic and muscarinic cholinergic receptors on spatial and passive avoidance learning/retention in rats. Daily pretraining test injections of combinations of the subthreshold doses of muscarinic (scopolamine 0.3 mg/kg) and nicotinic (mecamylamine 2.5 mg/kg or 10 mg/kg) antagonists impaired acquisition of the water-maze task (WM). Drug-induced deficits were also observed during the retention trial: the groups injected with scopolamine 0.3 mg/kg, mecamylamine 10 mg/kg and scopolamine 0.3 mg/kg in combination with mecamylamine 2.5 mg/kg showed reduced spatial bias compared with controls. Single preretention test injections of the combination of subthreshold doses of mecamylamine (10 mg/kg) and scopolamine (0.8 mg/kg) impaired memory retrieval in WM. Combined pretraining injections of subthreshold doses of scopolamine (1.0 mg/kg) and mecamylamine (10 mg/kg) induced a severe passive avoidance impairment comparable to 2.0 mg/kg of scopolamine. However, preretention test injections did not impair passive avoidance retention. Either single or combined injections of hexamethonium (5.0 mg/kg, SC) and methylscopolamine (1.0 mg/kg) did not impair either passive avoidance or water-maze performance. The present results suggest that 1) nicotinic and muscarinic systems jointly modulate performance in spatial and avoidance learning tasks and 2) cholinergic antagonists affect acquisition functions more effectively than retention ability. These findings may be relevant to the clinical disorders, like Alzheimer's disease, which are associated with a loss of both cholinergic neurons and nicotinic receptors.