A single, clinically relevant dose of the GABA_B agonist baclofen impairs visuomotor learning

Abstract

Baclofen is a GABA B agonist prescribed as a treatment for spasticity in stroke, brain injury and multiple sclerosis patients, who are often undergoing concurrent motor rehabilitation. r Decreasing GABAergic inhibition is a key feature of motor learning and so there is a possibility that GABA agonist drugs, such as baclofen, could impair these processes, potentially impacting rehabilitation. r Here, we examined the effect of 10 mg of baclofen, in 20 young healthy individuals, and found that the drug impaired retention of visuomotor learning with no significant effect on motor sequence learning. r Overall baclofen did not alter transcranial magnetic stimulation-measured GABA B inhibition, although the change in GABA B inhibition correlated with aspects of visuomotor learning retention. r Further work is needed to investigate whether taking baclofen impacts motor rehabilitation in patients.

Dissecting the chain of information processing and its interplay with neurochemicals and fluid intelligence across development

“…Besides these discrepancies, our findings in the mature participants suggest that lower GABA concentration within the IPS is associated with enhanced visuomotor processing, thus extending the involvement of GABA in the acquisition of visuomotor abilities. In addition to our suggestion of the involvement of developmental GABA in visuomotor processing, administration of GABA B agonist baclofen was shown to impair visuomotor processing in healthy adults (60). Consistent with this, we showed here that elevated GABA levels in the IPS are associated with poor visuomotor processing in later developmental stages.…”

Age‐related decline in cortical inhibitory tone strengthens motor memory

“…Second, it is well-established that the central nervous system includes at least two distinct forms of GABAergic inhibition: a tonic one involving (mostly extrasynaptic) metabotropic GABA A receptors, and a phasic one involving (mostly intrasynaptic) ionotropic GABA B receptors. Although resting MRS-GABA signal is thought to predominantly reflect the former ( Stagg, Bestmann, Constantinescu, Moreno Moreno, Allman, Mekle, Woolrich, Near, Johansen-Berg, Rothwell, 2011 , Stagg, Best, Stephenson, O’Shea, Wylezinska, Kincses, Morris, Matthews, Johansen-Berg, 2009 ), the latter may also explain some of the inter-individual variance in signal, and is known to play a role in adaptation memory ( Johnstone et al., 2021 ). The extent to which tonic versus phasic GABAergic signalling contributes to our findings therefore remains an open question for future research.…”

Differences in outcomes following an intensive upper-limb rehabilitation program for patients with common central nervous system-acting drug prescriptions

“…Several studies have previously reported a correlational link between high GABA concentration, 27 or receptor activity, 28,29 and worse functional outcomes from rehabilitation post-stroke. Furthermore, a single dose of the GABA B agonist baclofen impairs aspects of motor learning in healthy humans 30 ; and GABA antagonists can improve post-stroke motor recovery in rats. 13,14 Given these findings, and another early retrospective study finding a negative impact of benzodiazepine prescription on motor function recovery 16 (though see Hesse and Werner 31 ), caution has previously been advised in the prescription of GABA agonists, particularly benzodiazepines, post-stroke.…”