Neurochemical analysis of rat strain differences in the startle gating-disruptive effects of dopamine agonists

The disruption of prepulse inhibition (PPI) in rats by dopamine (DA) agonists is used to study the neural basis of strain differences in dopaminergic function. We reported that, compared to Long-Evans (LEH) rats, Sprague-Dawley (SDH) rats are more sensitive to the PPI-disruptive effects of the direct D1/D2 agonist apomorphine (APO) and the indirect DA agonist d-amphetamine (AMPH). This strain difference is heritable, with PPI drug sensitivity following a generational pattern (SDH>N2>F1>LEH) suggestive of additive effects of multiple genes. Here, we assessed the neurochemical bases for these heritable strain differences by measuring tissue levels of dopamine, serotonin (5HT) and their respective metabolites in several forebrain regions after vehicle, APO or AMPH administration. SDH rats were more sensitive than LEH rats to the PPI-disruptive effects of both APO (0.5 mg/kg) and AMPH (4.5 mg/kg). Several significant SDH vs. LEH strain differences in regional neurochemical levels were detected, as were drug effects on these chemicals. However, SDH, LEH and F1 rats did not exhibit differential drug sensitivity in any neurochemical indices measures. These findings suggest that inherited differences in the dopaminergic regulation of sensorimotor gating do not likely reflect differences in presynaptic forebrain dopaminergic or serotonergic processes.