Nicotinic acetylcholine receptors are possible therapeutic targets for schizophrenia

Abstract

The rate of smoking in patients with schizophrenia is higher than that in the general population. Nicotinic acetylcholine receptors (nAChR) are involved in the sensorimotor gating deficits in schizophrenia. We have revealed that nicotine ameliorates the disruption of the PPI, a model of sensorimotor gating, which is induced by apomorphine, a dopamine receptor agonist, but is not effective for the disruption of the PPI induced by phencyclidine, a glutamine NMDA receptor antagonist, in rats. Furthermore, the ameliorating effect of nicotine is antagonized by methyllycaconitine, a selective α7 nAChR antagonist. The effect of nocitine was also investigated in the stereotyped behavior induced by apomorphine, however, nicotine was found to have no significant effect. Considering these results, the ameliorating effect of the disruption of the PPI via α7 nAChR is therefore thought to be involved in dopaminergic systems. The dopaminergic systems involved in α7 nAChR may be different from the systems involved in stereotypy. In addition, this review describes the effects of the α7 nicotinic receptor agonists. © 2009 The Pharmaceutical Society of Japan.