Psychopharmacology (2010) 208:469–474 Electromyographic recordings The electromyogram (EMG) was recorded using sintered 11 × 17-mm active Ag–AgCl electrodes with the ActiveTwo system (BioSemi, Amsterdam, The Netherlands) relative to the common mode sense in a belly–tendon arrangement. The MEP was recorded from the left and right abductor pollicis brevis (APB). The active electrode was placed over the muscle belly of the APB. The reference electrode was placed over the proximal phalanx of the thumb. The ground electrode was attached to the wrist. EMG signal was digitized at 16 kHz, low-pass filtered (−3dB cutoff frequency 3,334 Hz; roll-off 30 dB/octave), and offline high-pass filtered (−3dB cutoff frequency 20 Hz; roll-off 48 dB/octave). Procedure In the present crossover design, participants received either a single dose of alcohol or placebo on one of the two occasions in a randomized counterbalanced order. Prior to the testing sessions and on a separate day, participants were invited upon the laboratory. A safety-screening list was administered to check for contraindications to TMS (Keel et al. 2001), and health was checked with a standard interview. In addition, safety issues and experimental procedures were explained to the subject, and written informed consent was obtained. Alcohol abuse and alcohol dependence were indexed with the AUDIT (Berner et al. 2007), and participants with AUDIT scores of 0 or >8 were excluded. Right handedness was assessed with the Edin- burgh handedness inventory (Oldfield 1971). Resting MT was determined using the standardized motor threshold estimation procedure (Schutter and van Honk 2006; see Table 1 for details). Participants were instructed to refrain from consuming alcoholic beverages 24 h prior to the testing session, not to consume coffee, tea, or chocolate 5 h before testing and to use their last meal at least 2 h prior to the testing session. To control for circadian rhythms, both testing sessions were conducted at the same time of the day. Each testing session 471 was separated by at least 24 h. Moreover, to minimize the effects of additional hormonal influences, female participants were not tested during the stopping week. Each experimental session started with a BAC measure- ment to ascertain sobriety after which participants con- sumed the alcoholic solution or placebo. Participants had 2 min to drink the solution while keeping their nose closed with their hand. The time between administration and paired-pulse TMS was approximately 30 min. During this period, EMG electrodes were attached to the left and right APB, and the optimal target sites for TMS were deter- mined. TCI was measured when the BAC curve approximat- ed 0.5‰ on the descending limb of the BAC curve (Verster et al. 2002). At the end of the final session, participants were debriefed and paid for participation. Both testing sessions took approximately 1 h to complete. Data reduction and analysis MEP amplitude was quantified as the peak-to-peak amplitude of the maximal EMG response. Left-to-right (l-rTCI) and right-to-left transcallosal inhibition (r-lTCI) were expressed according to the formulas [(1− (cMEPright/uMEPright))× 100] and [(1− (cMEPleft/uMEPleft))× 100], respectively. A general linear model (GLM) for repeated measure- ments with drug (alcohol versus placebo) and TCI (left to right versus right to left) as within-subjects factor and sex (female and male) as a between-subjects factor was run to examine the alcohol-related effects and possible sex differ- ences on TCI. To rule out possible alcohol-related effects of single-pulse TMS on TCI, an additional GLM for repeated measurements with drug (alcohol versus placebo) and side (left versus right hemisphere) as within-subjects factors and sex (female versus male) as a between-subjects factor was performed. Finally, to exclude effects of baseline EMG activity on TCI, a 2 × 2 GLM for repeated measurements with drug (alcohol versus placebo) and EMG (left versus right hand) as within-subjects factor and sex (female versus male) as within-subjects factor was conducted. The alpha level of significance was set at 0.05 (two-tailed). Table 1 Main demographics and characteristics of the participants Results Age (in years) AUDIT MT left hemisphere MT right hemisphere Handedness MT motor threshold Males (mean ± SEM) Females (mean ± SEM) 23.3±1.4 6.4 ±0.6 47.5±2.8 45.2±2.7 45.5±0.7 21.9± 1.1 5.8± 0.6 49± 2.0 47.8± 2.2 46.3± 0.7 p 0.43 0.53 0.66 0.47 0.44 BAC values did not differ between males (mean ± SD, 0.69± 0.04) and females (mean ± SD, 0.603±0.05; p= 0.17). Our hypothesis that alcohol would reduce TCI in both males and females was not confirmed (F(1, 21) = 2,752, p= 0.113). In contrast, a significant drug × sex interaction (F(1, 21) = 4.95; p = 0.038) was observed. Post hoc analyses demon- strated that alcohol significantly reduced TCI in females (F(1, 11) = 12.52; p = 0.005; ηp2 = 0.53) but not in males (F(1, 9) = 0.10; p = 0.76; Fig. 1).