Amphetamine effects on startle gating in normal women and female rats

Abstract

Background: Dopamine agonists disrupt prepulse inhibition (PPI) of startle in male rodents. In humans, this is observed only in some studies. We reported that PPI was disrupted by d-amphetamine in men, but only among those with high basal PPI levels. Here, amphetamine effects on PPI were tested in normal women and female rats. Materials and methods: Acoustic startle and PPI were tested in normal women after placebo or 20 mg amphetamine, in a double-blind, crossover design, and in female rats after vehicle or 4.5 mg/kg amphetamine. Rats were from Sprague-Dawley (SD) and Long Evans (LE) strains that differ significantly in gene expression in PPI-regulatory circuitry, including levels of nucleus accumbens (NAC) catechol-O-methyl transferase (COMT) mRNA. Results: Amphetamine was bioactive in humans based on quantitative autonomic and self-rating measures, but did not significantly change startle magnitude or PPI across all subjects. Amphetamine's effects on PPI in women correlated significantly (p∈