Opposite effects of tolcapone on amphetamine-disrupted startle gating in low vs. high COMT-expressing rat strains

The impact of COMT inhibition on AMPH-modified PPI was categorically different in strains exhibiting low vs. high levels of forebrain Comt expression, consistent with reports in humans that tolcapone has opposite effects on PPI among individuals with polymorphisms conferring low vs. high COMT activity. The present model provides a basis for understanding the mechanisms by which the effects of COMT inhibition on sensorimotor gating - and potentially, related neurocognitive and clinical functions - under hyperdopaminergic states are dependent on an individual's basal levels of COMT activity.