The effects of pimozide and phenoxybenzamine pretreatments on amphetamine and apomorphine potentiation of the acoustic startle response in rats

Abstract

A series of three experiments investigated the individual roles of neurons containing dopamine (DA) and norepinephrine (NE) in modulating the amplitude of the acoustic startle response (ASR) in rats. Experiment I investigated the effects of 0.1, 0.5, and 2.5 mg/kg pimozide or 5, 10, and 20 mg/kg phenoxybenzamine alone on startle amplitude. Experiments II–III investigated the effects of pretreatment with either 2.5 mg/kg pimozide or 10 mg/kg phenoxybenzamine on the potentiation of startleamplitude by either d-amphetamine (8 mg/kg), l-amphetamine (32 mg/kg), or apomorphine (3 mg/kg). Treatment with pimozide (2.5 mg/kg given 85 min before testing) and phenoxybenzamine (10 mg/kg, given 25 min before testing) resulted in a significant reduction in startle amplitude, supporting the conclusion that neurons containing NE and DA both tonically facilitate the ASR. The startlepotentiating effect of d- and l-amphetamine and apomorphine were totally blocked by pretreatment with pimozide (2.5 mg/kg, injected 2 h before these drugs), which supports the hypothesis that these agents potentiate startle at least in part by acting through dopaminergic neural systems. Phenoxybenzamine pretreatment (10 mg/kg, given 0.5 h before) also blocked the startle-potentiating effects of l-amphetamine and apomorphine, which suggests that noradrenergic neural systems are also involved in the potentiation of ASR by these agents, possibly through the interaction of dopaminergic and noradrenergic neural systems. The potentiating effect of d-amphetamine on ASR magnitude was not attenuated by phenoxybenzamine.