Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany.
Department of Psychology, University of Bonn, Bonn, Germany.
J Psychopharmacol. 2021 Jan;35(1):91-99. doi: 10.1177/0269881120972424. Epub 2020 Dec 4.
Benzodiazepines have reliable adverse effects on saccadic eye movements, but the impact of sex as a potential modulator of these effects is less clear. A recent study reported stronger adverse effects on the spatial consistency of saccades in females, which may reflect sex differences in cerebellar mechanisms.
We aimed to further examine the role of sex as a potential modulator of benzodiazepine effects by employing the saccadic adaptation paradigm, which is known to be sensitive to cerebellar functioning.
A total of =50 healthy adults performed a horizontal step prosaccade task and a saccadic adaptation task under 0.5 mg lorazepam, 1 mg lorazepam and placebo in a double-blind, within-subjects design.
In the prosaccade task, lorazepam had adverse effects on measures of peak velocity, latency and spatial consistency. The administration of 0.5 mg lorazepam led to significant reductions in gain-decrease adaptation, while a dose of 1 mg did not impair adaptation learning. Gain-increase adaptation was generally less pronounced, and unaffected by the drug. There were no significant drug×sex interactions in either task.
We conclude that a low dose of lorazepam impairs gain-decrease adaptation independent of sex. At higher doses, however, increasing fatigue may facilitate adaptation and thus counteract the adverse effects observed at lower doses. With regards to prosaccades, our findings confirm peak velocity as well as latency and spatial measures as sensitive biomarkers of GABAergic effects.
苯二氮䓬类药物对眼跳运动有可靠的不良反应,但性别作为这些影响的潜在调节剂的作用尚不清楚。最近的一项研究报告称,女性的眼跳空间一致性受到更强的不良反应,这可能反映了小脑机制中的性别差异。
我们旨在通过使用眼跳适应范式进一步研究性别作为苯二氮䓬类药物作用的潜在调节剂的作用,该范式已知对小脑功能敏感。
共有 50 名健康成年人在双盲、自身对照设计下,分别接受 0.5mg 劳拉西泮、1mg 劳拉西泮和安慰剂,完成水平跨步正眼跳任务和眼跳适应任务。
在正眼跳任务中,劳拉西泮对峰值速度、潜伏期和空间一致性的测量值有不良影响。给予 0.5mg 劳拉西泮导致增益减少适应显著降低,而 1mg 剂量不会损害适应学习。增益增加适应通常不太明显,且不受药物影响。在两项任务中,均未观察到药物×性别相互作用。
我们的结论是,低剂量的劳拉西泮会损害增益减少适应,而与性别无关。然而,在更高的剂量下,增加的疲劳可能会促进适应,从而抵消在较低剂量下观察到的不良反应。关于正眼跳,我们的发现证实了峰值速度以及潜伏期和空间测量值作为 GABA 能作用的敏感生物标志物。