Effects of GABA(A) and GABA(B) 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 50ms was significantly strengthened, and obtained also at ISIs between 100 and 200ms. 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 GABA(B) receptors. GABA(A)-ergic medication resulted in attenuation of l-IHI. Regarding s-IHI, our results are inconclusive and require further investigation.


CONCLUSIONS
This is the first human study evaluating the effect of baclofen on IHI, indicating that l-IHI is mediated by GABA(B)-ergic neurones. Because interhemispheric interaction is now also been used as a therapeutic approach, understanding the underlying neurotransmitter systems will be increasingly relevant.
Irlbacher
K
K
Vision and Motor Group, Department of Neurology, Charité, Humboldt University of Berlin, Campus Mitte, Schumannstrasse 20-21, D-10117 Berlin, Germany. kerstin.irlbacher@charite.de
Brocke
J
J
Mechow
J V
JV
Brandt
S A
SA
D000328:Adult; D001418:Baclofen / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003337:Corpus Callosum / Q000187:drug effects / Q000378:metabolism; D004558:Electric Stimulation; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D006801:Humans; D008297:Male; D008874:Midazolam / Q000494:pharmacology; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D012016:Reference Values; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D008874:Midazolam