Psychopharmacology (2009) 205:689–698 medical conditions, a modified structured clinical interview for DSM disorders (non-patient edition; SCID; First et al. 1997) to rule out Axis I diagnoses, and completed a urine toxicology test with exclusion for any illicit drug. Audi- ometry confirmed hearing threshold <40 dB(A) at 1,000 Hz. Subjects also completed a limited test of the acoustic startle reflex to screen for a minimum eyeblink startle magnitude of 50 units (1.22 µV/unit) using 118 dB (A), 40 ms noise pulses. Subjects completed the following questionnaires: (1) the Tridimensional Personality Questionnaire (TPQ; Cloninger 1987) to assess the relationship between novelty-seeking scores (NS) and sensitivity to the effects of pramipexole on PPI, based on reports that high NS individuals are most sensitive to the PPI-disruptive effects of indirect DA agonists (Hutchison et al. 1999; Talledo et al. 2009) and the PPI-enhancing effects of antipsychotics (Swerdlow et al. 2006); (2) the Sensation Seeking Scale (SSS; Zuckerman et al. 1972), based on reported increased sensitivity to DA agonists in individuals scoring high on this measure (Hutchison et al. 1999); and (3) the Eysenck Personality Questionnaire (EPQ) (Eysenck and Eysenck 1994). Sub- jects who passed screening criteria were tested 6–8 days later and retested 6–8 days after their first experimental session. The study had a two-test within-subject design for each dose of pramipexole. In other words, one group of subjects (n =20) was tested with placebo and 0.125 mg pramipexole, and a second group of subjects (n = 20) was tested with placebo and 0.1875 mg pramipexole. On test days, subjects arrived at 0830 hours and ate a standardized breakfast, and pramipexole (0.125 or 0.1875 mg; Boehringer Ingelheim GmbH, Ingelheim, Germany) or placebo was administered at 0930 hours. Startle testing began 60 min after pill administration. Heart rate and blood pressure were deter- mined (sitting position and brachial cuff), and subjects completed a symptom rating scale every 30–45 min; the first one occurred before pill ingestion. Symptom-rating visual analog scales (VAS) were designed to assess general somatic and psychological symptoms and level of con- sciousness (modified from Norris 1971; Bond and Lader 1974; Bunney et al. 1999). Subjects made a single, vertical mark representing their current state along a 100-mm line (0 mm represents “not true” and 100 mm represents “true”). Ratings assessed several states: “happy,” “queasy,” “dizzy,” “drowsy,” and perceptual sensitivity. Details of these rating scales are found in Swerdlow et al. (2002) and included prompts such as “Normal sounds seem unusually intense or loud.” For startle testing, subjects sat upright and were directed to look straight ahead and to stay awake. Two miniature Ag/AgCl electrodes were positioned below and to the outer canthus of each eye over orbicularis oculi; ground electrode 691 was positioned behind the left ear (R< 10 kΩ ). Electromyo- graphic activity was band-pass-filtered (1–1,000 Hz) and 60-Hz notch-filtered, and digitized, and 250 1-ms readings were recorded starting at startle stimulus onset. Acoustic startle stimuli were delivered by Telephonics (TDH-39-P, Maico) headphones. A background 70 dB(A) white noise was continuous throughout the session. Test sessions began with a 3-min acclimation period; during this period, the number of spontaneous eyeblinks were counted by a remote observer using a RadioShack security camera system (model 49-2513) (inter-observer R= 0.97). This was fol- lowed by 42 trials with six conditions repeated in pseudorandom order: a 118-dB(A), 40-ms noise burst alone (pulse alone) and the same 118-dB(A), 40-ms noise burst preceded 10, 20, 30, 60, or 120 ms by a prepulse (5-ms burst) 16 dB over background. A variable inter-trial interval averaged 20 s (15–25 s). The test session was structured identically to that described in our previous studies of DA agonist effects on PPI in humans (Swerdlow et al. 2003b; Talledo et al. 2009). On completion of this startle test, additional autonomic and subjective rating measurements were obtained, as were additional “pilot” psychophysiolog- ical measures, including a visual latent inhibition task. Data from these subsequent tests are not included in this analysis. The primary reasons for disqualification were that subjects had low screening startle magnitude (n = 22), withdrew from testing prior to the second test day (n = 3), or had a SCID-based diagnosis (n = 14; First et al. 1997); others included positive urine toxicology for illicit drugs (n = 2). PPI was defined as [100-(100 × magnitude on prepulse trial/magnitude on pulse alone trial)]. Screening PPI across all 40 subjects was normally distributed [mean (SD)% across all intervals (10–120 ms) = 9.33 (20.25); median= 7.68; skewness = 0.27; kurtosis = 0.17]. Startle magnitude, latency, and PPI were analyzed with mixed-design analyses of variance (ANOVAs), with trial type and pramipexole dose (placebo vs. active) as within-subject factors, and dose groups [i.e., subjects tested with placebo vs. 0.125 mg pramipexole (“0.125 mg group”) and subjects tested with placebo vs. 0.1875 mg pramipexole (“0.1875 mg group”)] as the between-subject factor. Separate analyses were then pursued on each dose group. No consistent drug interac- tions were noted with eye side (left vs. right), and thus, main effects of eye side and interactions are not reported. “Baseline PPI” was defined as the mean %PPI for 60- and 120-ms prepulse intervals on the screening day, as described previously (Swerdlow et al. 2009). Personality scales previously found to be related to drug effects on PPI were treated as continuous variables: the total novelty- seeking score (NS) from the TPQ, total and disinhibition subscale scores from the SSS, and extraversion subscale