696 Table 3 Peak reflex latency and habituation Prepulse Interval (ms) 0a 10 20 30 60 120 First block Last block a Pulse alone trials Psychopharmacology (2009) 205:689–698 0.125 mg group Placebo Active dose Peak startle latency (ms) [mean (SEM)] 60.9 (1.6) 61.4 (2.0) 56.9 (1.6) 58.3 (2.2) 55.9 (1.8) 56.7 (2.2) 54.2 (1.8) 55.9 (2.1) 52.5 (1.8) 54.0 (2.1) 57.2 (1.3) 56.9 (2.0) Startle magnitude on pulse alone trials [mean (SEM)] 117.2 (16.0) 116.7 (17.9) 81.6 (14.7) 73.1 (16.9) 0.1875 mg group Placebo 63.5 (1.2) 59.7 (1.3) 59.7 (1.3) 56.6 (1.2) 54.0 (1.4) 58.6 (1.3) 145.9 (19.2) 87.8 (16.6) Active Dose 62.1 (1.0) 59.3 (1.2) 58.5 (0.9) 57.4 (0.9) 54.9 (1.6) 59.1 (1.2) 144.6 (19.2) 92.5 (19.5) effects of the indirect DA agonist amphetamine (Hutchison et al. 1999; Talledo et al. 2009), the effects of pramipexole were not moderated by personality measures of novelty- seeking, sensation-seeking, disinhibition, or extraversion; unlike the PPI-modulatory effects of either amphetamine Fig. 4 Effects of pramipexole on startle magnitude (inset; mean± SEM) and %PPI (mean ±SEM) across all trial conditions in three groups of rats administered placebo vs. 0.1 mg/kg pramipexole (n=8), placebo vs. 0.3 mg/kg pramipexole (n=8) or placebo vs. 1.0 mg/kg mg pramipexole (n=8). Open circle Placebo; closed circle active dose. Insert, asterisk startle reducing effects of 1.0 mg/kg pramipexole (p< 0.035). Main figure, number sign PPI-enhancing effects of pramipex- ole at 10–20-ms prepulse intervals for 0.1 and 0.3 mg/kg doses (p= 0.02); asterisk PPI-reducing effects of 0.3 and 1.0 mg/kg pramipexole (p<−0.008–0.03) (Swerdlow et al. 2003b; Talledo et al. 2009), direct D2/D3 agonists (Bitsios et al. 2005), or the NMDA antagonist/DA releaser memantine (Swerdlow et al. 2009), these effects of pramipexole were independent of baseline PPI levels. The fact that pramipexole effects on PPI differ from those of other DA agonists is consistent with preclinical evidence in rats and humans. In rats, PPI-reducing effects of pramipexole do not differ across strains that exhibit pronounced differences in sensitivity to the PPI-disruptive effects of amphetamine (Swerdlow et al. 2003b; Talledo et al. 2009) and mixed D2/D3 agonists (Swerdlow et al. 2001, 2004a, b, c; Weber et al. 2008). Furthernore, unlike amphetamine and mixed D2/D3 agonists, the PPI- disruptive effects of pramipexole in rats are relatively insensitive to selective D2 receptor blockade but are opposed by compounds with selective functional antago- nism at D3 receptors (Weber et al. 2009). Evidence for differences in the PPI-modifying effects of pramipexole vs. other DA agonists in humans comes from findings that personality dimensions and/or baseline PPI moderate the PPI-disruptive effects of amphetamine (Hutchison et al. 1999; Talledo et al. 2009) and mixed D2/D3 agonists (Bitsios et al. 2005) but not those of pramipexole (present study); this may suggest that these moderating effects primarily reflect activity at D2 and not D3 DA receptors. Pramipexole-induced PPI increases in humans were limited to the 120-ms prepulse intervals. Reflex inhibition at these longer intervals can be enhanced by attention directed at a continuous prepulse (Filion et al. 1993). While the present study utilized discrete (vs. continuous) prepulses and no attentional instructions were given, it is nonetheless possible that the mechanisms responsible for pramipexole’s enhancement of “attentionally sensitive” inhibition reflect its action on brain mechanisms that regulate attention. No significant correlations were detected between increases in