Amphetamine effects on startle gating in normal women and female rats |
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Authors: | Jo A Talledo Ashley N Sutherland Owens Tijmen Schortinghuis Neal R Swerdlow |
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Institution: | (1) Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA |
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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 < 0.0008) with placebo PPI levels (reducing PPI only in women whose basal PPI levels exceeded the sample median) and with
measures of novelty and sensation seeking. Amphetamine decreased PPI in SD rats that have relatively low NAC COMT gene expression
and increased PPI in LE rats that have relatively high NAC COMT gene expression.
Conclusion The dopaminergic regulation of PPI in humans is related to basal levels of sensorimotor gating and to specific personality
traits in normal men and women. In rats, the effects of amphetamine on PPI differ significantly in strains with low vs. high
NAC COMT expression. |
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Keywords: | Amphetamine Dopamine Prepulse inhibition Sensorimotor gating Startle Strains |
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