[Nicotinic acetylcholine receptors are possible therapeutic targets for schizophrenia].
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 alpha7 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 alpha7 nAChR is therefore thought to be involved in dopaminergic systems. The dopaminergic systems involved in alpha7 nAChR may be different from the systems involved in stereotypy. In addition, this review describes the effects of the alpha7 nicotinic receptor agonists.
Kohnomi
Shuntaro
S
Department of Clinical Pharmaceutical Science, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
Suemaru
Katsuya
K
Kawasaki
Hiromu
H
Choshi
Tominari
T
Hibino
Satoshi
S
Araki
Hiroaki
H
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology; D020233:Gait Disorders, Neurologic / Q000188:drug therapy; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D009433:Neural Inhibition; D009538:Nicotine / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011978:Receptors, Nicotinic / Q000502:physiology*; D012559:Schizophrenia / Q000209:etiology*; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D013239:Stereotyped Behavior / Q000187:drug effects; D000077526:Tropisetron; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000932:Antiemetics; C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat; D007211:Indoles; D011978:Receptors, Nicotinic; D012702:Serotonin Antagonists; D064569:alpha7 Nicotinic Acetylcholine Receptor; D000077526:Tropisetron; D009538:Nicotine; D004298:Dopamine