Nicotine blocks apomorphine-induced disruption of prepulse inhibition of the acoustic startle in rats: possible involvement of central nicotinic alpha7 receptors

Abstract

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. Over the dose range tested, nicotine (0.05-1 mg kg(-1), s.c.) did not disrupt PPI. Neither methyllycaconitine (0.5-5 mg kg(-1), s.c.), an alpha(7) nicotinic receptor antagonist, nor dihydro-beta-erythroidine (0.5-2 mg kg(-1), s.c.), an alpha(4)beta(2) nicotinic receptor antagonist, had any effect on PPI. Nicotine (0.01-0.2 mg kg(-1), s.c.) dose-dependently reversed the disruption of PPI induced by apomorphine (1 mg kg(-1), s.c.), but had no effect on the disruption of PPI induced by phencyclidine (2 mg kg(-1), s.c.). The reversal of apomorphine-induced PPI disruption by nicotine (0.2 mg kg(-1)) was eliminated by mecamylamine (1 mg kg(-1), i.p.), but not by hexamethonium (10 mg kg(-1), i.p.), indicating the involvement of central nicotinic receptors. The antagonistic action of nicotine on apomorphine-induced PPI disruption was dose-dependently blocked by methyllycaconitine (1 and 2 mg kg(-1), s.c.). However, dihydro-beta-erythroidine (1 and 2 mg kg(-1), s.c.) had no effect. These results suggest that nicotine reverses the disruption of apomorphine-induced PPI through central alpha(7) nicotinic receptors.

Figure 1

Lack of effects of nicotine, MLA and DHβE on PPI in rats. Nicotine was administered 30 min before the measurement of PPI. MLA or DHβE was administered 45 min before the measurement. Each point represents the mean PPI of eight rats in the PP70-P (70 dB prepulse followed by 120 dB pulse) and PP80-P (80 dB prepulse followed by 120 dB pulse) trials. The vertical lines represent±s.e.m.

Figure 2

Effects of nicotine and haloperidol on apomorphine-induced disruption of PPI in rats. Apomorphine was injected 15 min before the measurement of PPI. Nicotine or haloperidol was administered 15 min before the apomorphine injection. Each column represents the mean PPI with s.e.m. in the PP70-P (70 dB prepulse followed by 120 dB pulse) and PP80-P (80 dB prepulse followed by 120 dB pulse) trials (n=8). ^**P<0.01 compared with the naive group (two-way ANOVA followed Student's t-test). ^#P<0.05, ^##P<0.01 compared with the apomorphine-alone group (two-way ANOVA followed by Dunnett's test).

Figure 3

Effects of nicotinic receptor antagonists on the reversal of apomorphine-induced PPI disruption by nicotine in rats. Apomorphine, nicotine and nicotinic receptor antagonists were administered 15, 30 and 45 min before the measurement of PPI, respectively. Each column represents the mean PPI with s.e.m. in the PP70-P (70 dB prepulse followed by 120 dB pulse) and PP80-P (80 dB prepulse followed by 120 dB pulse) trials (n=8). ^**P<0.01 compared with the naive group (two-way ANOVA followed by Student's t-test). ^#P<0.05, ^##P<0.01 compared with the apomorphine-alone group (two-way ANOVA followed by Dunnett's test). ^†P<0.05, ^††P<0.01 compared with the apomorphine+nicotine group (two-way ANOVA followed by Dunnett's test or Student's t-test). Mec, mecamylamine; Hex, hexamethonium.

Figure 4

Effects of nicotine, haloperidol and clozapine on phencyclidine-induced disruption of PPI in rats. All drugs were administered 30 min before the measurement of PPI. Each column represents the mean PPI with s.e.m. in the PP70-P (70 dB prepulse followed by 120 dB pulse) and PP80-P (80 dB prepulse followed by 120 dB pulse) trials (n=8). ^**P<0.01 compared with the naive group (two-way ANOVA followed by Student's t-test). ^##P<0.01 compared with the phencyclidine-alone group (two-way ANOVA followed by Dunnett's test).