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 GABAB receptors, and (ii) GABAA-ergic neurones mediate early IHI, whereas GABAB-ergic neurones mediate later IHI. In humans the mechanism is unclear. Interactions between cortical inhibitory circuits suggest a postsynaptic GABAB-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 GABAB-agonist (baclofen) in 17 subjects, and (ii) a GABAA-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.