title: Effects of GABA(A) and GABA(B) agonists on interhemispheric inhibition in man.
abstract: 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.
authors.affiliation: 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
authors.forename: K
authors.initials: K
authors.lastname: Irlbacher
authors.forename: J
authors.initials: J
authors.lastname: Brocke
authors.forename: J V
authors.initials: JV
authors.lastname: Mechow
authors.forename: S A
authors.initials: SA
authors.lastname: Brandt
mesh_terms: 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
chemical_list: 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