Clinical studies show that galantamine, a weak acetylcholine (ACh) esterase inhibitor and allosteric potentiator of nicotinic ACh receptors (nAChRs), improves negative and cognitive symptoms in schizophrenia, while donepezil, a potent ACh esterase inhibitor, does not. We have recently found that galantamine, but not donepezil, reversed isolation rearing-induced deficits of prepulse inhibition (PPI), sensory information-processing deficits, in mice. In addition, we unexpectedly found that the galantamine-induced improvements in PPI deficits were prevented by the muscarinic ACh receptor (mAChR) antagonists scopolamine and telenzepine (preferential for M₁ subtype), but not by the nAChR antagonists. Galantamine, like donepezil, increased extracellular ACh levels in the prefrontal cortex. However, donepezil, unlike galantamine, inhibited M₁-mAChR-mediated Ca²⁺ signal in human neuroblastoma SH-SY5Y. These results suggest that galantamine improves isolation rearing-induced PPI deficits via an activation of mAChRs and the difference in the effect on the PPI deficits between galantamine and donepezil is due to that in their action on M₁-mAChRs. The possible mechanisms for the beneficial effect of galantamine are discussed in a model of isolation rearing-induced PPI deficits.