Effects of GABAA and GABAB agonists on interhemispheric inhibition in man

Objective: Animal studies on neurotransmitter systems that mediate interhemispheric inhibition (IHI) suggest that, (i) callosal transmission is regulated by presynaptic GABA(B) receptors, and (ii) GABA(A)-ergic neurones mediate early IHI, whereas GABA(B)-ergic neurones mediate later IHI. In humans the mechanism is unclear. Interactions between cortical inhibitory circuits suggest a postsynaptic GABA(B)-ergic mechanism. We will here test this hypothesis. Methods: Short-latency IHI (s-IHI) and long-latency IHI (l-IHI) were evaluated using the paired pulse paradigm before and under medication with (i) a GABA(B)-agonist (baclofen) in 17 subjects, and (ii) a GABA(A)-agonist (midazolam) in 10 subjects participating twice. Results: Baclofen did not significantly enhance s-IHI. L-IHI between 20 and 50 ms was significantly strengthened, and obtained also at ISIs between 100 and 200 ms. Midazolam had no effect on s-IHI, whereas l-IHI was attenuated. Conclusions: Our results support the hypothesis, that l-IHI in humans is mediated by postsynaptic GABAB receptors. GABAA-ergic medication resulted in attenuation of l-IHI. Regarding s-IHI, our results are inconclusive and require further investigation. Significance: This is the first human study evaluating the effect of baclofen on IHI, indicating that l-IHI is mediated by GABAB-ergic neurones. Because interhemispheric interaction is now also been used as a therapeutic approach, understanding the underlying neurotransmitter systems will be increasingly relevant. (c) 2006 Published by Elsevier Ireland Ltd on behalf of International Federation of Clinical Neurophysiology.