A single, clinically relevant dose of the GABA(B) agonist baclofen impairs visuomotor learning

The GABA(B) agonist baclofen is taken daily as a treatment for spasticity by millions of stroke, brain injury and multiple sclerosis patients, many of whom are also undergoing motor rehabilitation. However, decreases in GABA are suggested to be a key feature of human motor learning, which raises questions about whether drugs increasing GABAergic activity may impair motor learning and rehabilitation. In this double-blind, placebo-controlled study, we investigated whether a single 10 mg dose of the GABA(B) agonist baclofen impaired motor sequence learning and visuomotor learning in 20 young healthy participants of both sexes. Participants trained on visuomotor and sequence learning tasks using their right hand. Transcranial magnetic stimulation (TMS) measures of corticospinal excitability, GABA(A) (short-interval intracortical inhibition, 2.5 ms) and GABA(B) (long-interval intracortical inhibition, 150 ms) receptor activation were recorded from left M1. Behaviourally, baclofen caused a significant reduction of visuomotor aftereffect (F (1,137.8) = 6.133, P = 0.014) and retention (F (1,130.7) = 4.138, P = 0.044), with no significant changes to sequence learning. There were no overall changes to TMS measured GABAergic inhibition with this low dose of baclofen. This result confirms the causal importance of GABA(B) inhibition in mediating visuomotor learning and suggests that chronic baclofen use could negatively impact aspects of motor rehabilitation.