Nicotine blocks apomorphine-induced disruption of prepulse inhibition of the acoustic startle in rats: possible involvement of central nicotinicα7receptors

Katsuya Suemaru, Kayo Yasuda, Kenta Umeda, Hiroaki Araki, Kazuhiko Shibata, Tominari Choshi, Satoshi Hibino, Yutaka Gomita
2004 British Journal of Pharmacology  
1 Nicotine has been reported to normalize deficits in auditory sensory gating in the cases of schizophrenia, suggesting an involvement of nicotinic acetylcholine receptors in attentional abnormalities. However, the mechanism remains unclear. The present study investigated the effects of nicotine on the disruption of prepulse inhibition (PPI) of the acoustic startle response induced by apomorphine or phencyclidine in rats. 2 Over the dose range tested, nicotine (0.05-1 mg kg À1 , s.c.) did not
more » ... srupt PPI. Neither methyllycaconitine (0.5-5 mg kg À1 , s.c.), an a 7 nicotinic receptor antagonist, nor dihydro-berythroidine (0.5-2 mg kg À1 , s.c.), an a 4 b 2 nicotinic receptor antagonist, had any effect on PPI. 3 Nicotine (0.01-0.2 mg kg À1 , s.c.) dose-dependently reversed the disruption of PPI induced by apomorphine (1 mg kg À1 , s.c.), but had no effect on the disruption of PPI induced by phencyclidine (2 mg kg À1 , s.c.). 4 The reversal of apomorphine-induced PPI disruption by nicotine (0.2 mg kg À1 ) was eliminated by mecamylamine (1 mg kg À1 , i.p.), but not by hexamethonium (10 mg kg À1 , i.p.), indicating the involvement of central nicotinic receptors. 5 The antagonistic action of nicotine on apomorphine-induced PPI disruption was dose-dependently blocked by methyllycaconitine (1 and 2 mg kg À1 , s.c.). However, dihydro-b-erythroidine (1 and 2 mg kg À1 , s.c.) had no effect. 6 These results suggest that nicotine reverses the disruption of apomorphine-induced PPI through central a 7 nicotinic receptors.
doi:10.1038/sj.bjp.0705855 pmid:15197106 pmcid:PMC1575066 fatcat:lfpmjrdupvc3bmm34qsy7drevm