The effect of SR 141716 and apomorphine on sensorimotor gating in Swiss mice.

The aim of the present study was to investigate in Swiss mice the acute effects of the CB(1) receptor antagonist N-piperidino-5-(4-chlorphenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (SR 141716) alone and in combination with apomorphine, a D(1)/D(2) receptor agonist, on prepulse inhibition (PPI) of the acoustic startle response, an operational measure of sensorimotor gating. SR 141716 (1 and 3 mg/kg i.p.) had no significant effect on PPI. Apomorphine (3 mg/kg i.p.) significantly disrupted PPI. The PPI of mice injected with SR 141716 (1 mg/kg i.p.) plus apomorphine (3 mg/kg i.p.) was not significantly different to that of vehicle plus apomorphine (3 mg/kg i.p.)-treated mice. However, the higher dose of SR 141716 used (3 mg/kg i.p.) significantly inhibited the disruption of PPI produced by apomorphine. These results suggest that antagonism of CB(1) receptors with SR 141716 has no significant effect on sensorimotor gating in Swiss mice. However, CB(1) receptors appear to be important in the effect of apomorphine on sensorimotor gating, as antagonism of CB(1) receptors with SR 141716 inhibits apomorphine-induced disruptions.