Effects of lorazepam on saccadic eye movements: the role of sex, task characteristics and baseline traits

• Published in: Journal of psychopharmacology (Oxford) 2018-06, Vol.32 (6), p.678-690
• Main Authors: Ettinger, Ulrich, Meyhöfer, Inga, Mehta, Mitul A, Kumari, Veena, Corr, Philip J, Williams, Steven CR, Perkins, Adam M
• Format: Article
• Language: English
• Subjects: Adult; Adults; Anti-Anxiety Agents - administration & dosage; Anti-Anxiety Agents - adverse effects; Anti-Anxiety Agents - pharmacology; Anxiety; Benzodiazepines; Benzodiazepines - administration & dosage; Benzodiazepines - adverse effects; Benzodiazepines - pharmacology; Biomarkers; Blindness; Brain stem; Cerebellum; Dose-Response Relationship, Drug; Double-Blind Method; Eye movements; Female; Females; Humans; Intelligence; Lorazepam; Lorazepam - administration & dosage; Lorazepam - adverse effects; Lorazepam - pharmacology; Male; Neostriatum; Saccades - drug effects; Saccadic eye movements; Sex; Sex Factors; Velocity; Young Adult
• ISSN: 0269-8811; 1461-7285
• DOI: 10.1177/0269881118772450

Background: Saccadic eye movements are controlled by a network of parietal, frontal, striatal, cerebellar and brainstem regions. The saccadic peak velocity is an established biomarker of benzodiazepine effects, with benzodiazepines reliably reducing the peak velocity. Aims: In this study, we aimed to replicate the effects of benzodiazepines on peak velocity and we investigated effects on previously less studied measures of saccades. We also explored the roles of sex, task characteristics and the baseline variables age, intelligence and trait anxiety in these effects. Method: Healthy adults (N = 34) performed a horizontal step prosaccade task under 1 mg lorazepam, 2 mg lorazepam and placebo in a double-blind, within-subjects design. Results: We replicated the dose-dependent reduction in peak velocity with lorazepam and showed that this effect is stronger for saccades to targets at smaller eccentricities. We also demonstrated that this effect is independent of sex and other baseline variables. Lorazepam effects were widespread, however, occurring on mean and variability measures of most saccadic variables. Additionally, there were sex-dependent lorazepam effects on spatial consistency of saccades, indicating more adverse effects in females. Conclusions: We conclude that saccadic peak velocity is a sensitive and robust biomarker of benzodiazepine effects. However, lorazepam has pronounced effects also on other parameters of horizontal saccades. Sex-dependent drug effects on spatial consistency may reflect cerebellar mechanisms, given the role of the cerebellum in saccadic spatial accuracy.