[Beneficial effect of galantamine on sensory information-processing deficits]

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 M(1) subtype), but not by the nAChR antagonists. Galantamine, like donepezil, increased extracellular ACh levels in the prefrontal cortex. However, donepezil, unlike galantamine, inhibited M(1)-mAChR-mediated Ca(2+) 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 M(1)-mAChRs. The possible mechanisms for the beneficial effect of galantamine are discussed in a model of isolation rearing-induced PPI deficits.