Amphetamine dose dependently disrupts prepulse inhibition of the acoustic startle response in rats within a narrow time window

Prepulse inhibition (PPI) of the acoustic startle response refers to the re duction in startle amplitude when a weak prepulse precedes a startle-induci ng pulse. Prepulse inhibition has been shown to be disrupted by amphetamine at doses that also stimulate locomotor activity, and it has been suggested that the same neuroanatomical substrate, mesolimbic dopamine activation, m ediates the effects of amphetamine on locomotor activity and PPI. Amphetami ne stimulates locomotor activity and mesolimbic dopamine release over a 1- to 3-h period, whereas PPI is typically measured within the first 30 min fo llowing amphetamine treatment. The present study therefore determined wheth er delays in testing would alter the PPI-disruptive effect of amphetamine i n male Wistar rats. Amphetamine dose dependently disrupted PPI when the tes t session occurred 10 min following amphetamine treatment and only when the prepulse intensity was 5-10 dB above background. Delays of 40 and 60 min p ost-amphetamine injection, however, resulted in a loss of the ability of am phetamine to disrupt PPI although locomotor activity was significantly stim ulated by amphetamine at these time points. The data from the present study therefore do not readily fit with the notion that the effects of amphetami ne on locomotion and PPI are mediated by the same substrate. (C) 1999 Elsev ier Science Inc.