Effects of lorazepam and baclofen on short- and long-latency afferent inhibition

The afferent volley evoked by peripheral nerve stimulation has an inhibitory influence on transcranial magnetic stimulation induced motor evoked potentials. This phenomenon, known as afferent inhibition, occurs in two phases: short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI). SAI exerts its inhibitory influence via cholinergic and GABAergic activity. The neurotransmitter receptors that mediate LAI remain unclear. The present study aimed to determine whether LAI is contributed by GABA(A) and/or GABA(B) receptor activity. In a double-blinded, placebo-controlled study, 2.5 mg of lorazepam (GABA(A) agonist), 20 mg of baclofen (GABA(B) agonist) and placebo were administered to 14 males (mean age 22.7 +/- 1.9 years) in three separate sessions. SAI and LAI, evoked by stimulation of the median nerve and recorded from the first dorsal interosseous muscle, were quantified before and at the peak plasma concentration following drug ingestion. Results indicate that lorazepam reduced LAI by similar to 40% and, in support of previous work, reduced SAI by similar to 19%. However, neither SAI, nor LAI were altered by baclofen. In a follow-up double-blinded, placebo-controlled study, 10 returning participants received placebo or 40 mg of baclofen (double the dosage used in Experiment 1). The results obtained indicate that SAI and LAI were unchanged by baclofen. This is the first study to show that LAI is modulated by GABA(A) receptor activity, similar to SAI, and that afferent inhibition does not appear to be a GABA(B) mediated process.