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The role of GABAB receptors in intracortical inhibition in the human motor cortex

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Abstract

While GABAB receptors are thought to have an important role in mediating long interval intracortical inhibition (LICI) in the human motor cortex, the effect of a selective GABAB receptor agonist on this measure has not been directly tested. Nine healthy volunteers ingested either 50 mg baclofen (BAC) or placebo (PBO) in a randomized, double blind crossover design, with the second session one week later. We used transcranial magnetic stimulation to assess motor threshold, motor evoked potential (MEP) amplitude, cortical silent period (CSP) duration, short interval intracortical inhibition (SICI) and LICI before and 90 min following drug intake. There was no specific effect of drug on motor threshold, MEP amplitude or CSP duration. BAC resulted in a significant increase in LICI (P=0.002) and a significant decrease in SICI (P=0.046) while PBO had no effect. Our findings demonstrate that the enhanced GABAB receptor activation results in differential effects on these two measures of intracortical inhibition in the human motor cortex. The increase in LICI is likely to be a result of increased GABAB receptor mediated inhibitory post-synaptic potentials, while the reduction in SICI may relate to the activation of pre-synaptic GABAB receptors reducing GABA release.

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References

  • Avoli M, Hwa G, Louvel J, Kurcewicz I, Pumain R, Lacaille JC (1997) Functional and pharmacological properties of GABA-mediated inhibition in the human neocortex. Can J Physiol Pharmacol 75:526–534

    Article  PubMed  CAS  Google Scholar 

  • Bowery NG (1993) GABAB receptor pharmacology. Annu Rev Pharmacol Toxicol 33:109–147

    PubMed  CAS  Google Scholar 

  • Caddick SJ, Hosford DA (1996) The role of GABAB mechanisms in animal models of absence seizures. Mol Neurobiol 13:23–32

    Article  PubMed  CAS  Google Scholar 

  • Chen R, Lozano AM, Ashby P (1999) Mechanism of the silent period following transcranial magnetic stimulation. Exp Brain Res 128:539–542

    Article  PubMed  CAS  Google Scholar 

  • Connors BW, Malenka RC, Silva LR (1988) Two inhibitory postsynaptic potentials, and GABAA and GABAB receptor- mediated responses in neocortex of rat and cat. J Physiol (Lond) 406:443–468

    CAS  Google Scholar 

  • Deisz RA (1999a) The GABA(B) receptor antagonist CGP 55845A reduces presynaptic GABA(B) actions in neocortical neurons of the rat in vitro. Neuroscience 93:1241–1249

    Article  CAS  Google Scholar 

  • Deisz RA (1999b) GABA(B) receptor-mediated effects in human and rat neocortical neurones in vitro. Neuropharmacology 38:1755–1766

    Article  CAS  Google Scholar 

  • Deisz RA, Billard JM, Zieglgansberger W (1997) Presynaptic and postsynaptic GABAB receptors of neocortical neurons of the rat in vitro: differences in pharmacology and ionic mechanisms. Synapse 25:62–72

    Article  PubMed  CAS  Google Scholar 

  • Di Lazzaro V, Restuccia D, Oliviero A, Profice P, Ferrara L, Insola A, Mazzone P, Tonali P, Rothwell JC (1998) Magnetic transcranial stimulation at intensities below active motor threshold activates intracortical inhibitory circuits. Exp Brain Res 119:265–268

    Article  PubMed  CAS  Google Scholar 

  • Di Lazzaro V, Oliviero A, Meglio M, Cioni B, Tamburrini G, Tonali P, Rothwell JC (2000) Direct demonstration of the effect of lorazepam on the excitability of the human motor cortex. Clin Neurophysiol 111:794–799

    Article  PubMed  CAS  Google Scholar 

  • Di Lazzaro V, Oliviero A, Saturno E, Dileone M, Pilato F, Nardone R, Ranieri F, Musumeci G, Fiorilla T, Tonali PA (2005a) Effects of lorazepam on short latency afferent inhibition and short latency intracortical inhibition in humans. J Physiol 564:661–668

    Article  CAS  Google Scholar 

  • Di Lazzaro V, Pilato F, Dileone M, Tonali PA, Ziemann U (2005b) Dissociated effects of diazepam and lorazepam on short latency afferent inhibition. J Physiol 569:315–323

    Article  CAS  Google Scholar 

  • Fisher RJ, Nakamura Y, Bestmann S, Rothwell JC, Bostock H (2002) Two phases of intracortical inhibition revealed by transcranial magnetic threshold tracking. Exp Brain Res 143:240–248

    Article  PubMed  CAS  Google Scholar 

  • Fuhr P, Agostino R, Hallett M (1991) Spinal motor neuron excitability during the silent period after cortical stimulation. Electroencephalogr Clin Neurophysiol 81:257–262

    Article  PubMed  CAS  Google Scholar 

  • Garvey MA, Ziemann U, Becker DA, Barker CA, Bartko JJ (2001) New graphical method to measure silent periods evoked by transcranial magnetic stimulation. Clin Neurophysiol 112: 1451–1460

    Article  PubMed  CAS  Google Scholar 

  • Hallett M (1995) Transcranial magnetic stimulation. Negative effects. Adv Neurol 67:107–113

    PubMed  CAS  Google Scholar 

  • Hanajima R, Ugawa Y, Terao Y, Sakai K, Furubayashi T, Machii K, Kanazawa I (1998) Paired-pulse magnetic stimulation of the human motor cortex: differences among I waves. J Physiol 509: 607–618

    Article  PubMed  CAS  Google Scholar 

  • Hanajima R, Furubayashi T, Iwata NK, Shiio Y, Okabe S, Kanazawa I, Ugawa Y (2003) Further evidence to support different mechanisms underlying intracortical inhibition of the motor cortex. Exp Brain Res 151:427–434

    Article  PubMed  Google Scholar 

  • Hill DR, Bowery NG (1981) 3H-baclofen and 3H-GABA bind to bicuculline-insensitive GABA B sites in rat brain. Nature 290:149–152

    Article  PubMed  CAS  Google Scholar 

  • Ilic TV, Meintzschel F, Cleff U, Ruge D, Kessler KR, Ziemann U (2002) Short-interval paired-pulse inhibition and facilitation of human motor cortex: the dimension of stimulus intensity. J Physiol 545.1:153–167

    Article  CAS  Google Scholar 

  • Inghilleri M, Berardelli A, Marchetti P, Manfredi M (1996) Effects of diazepam, baclofen and thiopental on the silent period evoked by transcranial magnetic stimulation in humans. Exp Brain Res 109:467–472

    Article  PubMed  CAS  Google Scholar 

  • Jones EG (1993) GABAergic neurons and their role in cortical plasticity in primates. Cereb Cortex 3:361–372

    Article  PubMed  CAS  Google Scholar 

  • Kujirai T, Caramia MD, Rothwell JC, Day BL, Thompson PD, Ferbert A, Wroe S, Asselman P, Marsden CD (1993) Corticocortical inhibition in human motor cortex. J Physiol (Lond) 471:501–519

    CAS  Google Scholar 

  • McCormick DA (1989) GABA as an inhibitory neurotransmitter in human cerebral cortex. J Neurophysiol 62:1018–1027

    PubMed  CAS  Google Scholar 

  • Nakamura H, Kitagawa H, Kawaguchi Y, Tsuji H (1997) Intracortical facilitation and inhibition after transcranial magnetic stimulation in conscious humans. J Physiol (Lond) 498:817–823

    CAS  Google Scholar 

  • Rossini PM, Barker AT, Berardelli A, Caramia MD, Caruso G, Cracco RQ, Dimitrijevic MR, Hallett M, Katayama Y, Lücking CH, Maertens de Noordhout A, Marsden CD, Murray NMF, Rothwell JC, Swash M, Tomberg C (1994) Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee. Electroencephalogr Clin Neurophysiol 91:79–92

    Article  PubMed  CAS  Google Scholar 

  • Sander T, Samochowiec J, Ladehoff M, Smolka M, Peters C, Riess O, Rommelspacher H, Schmidt LG (1999) Association analysis of exonic variants of the gene encoding the GABAB receptor and alcohol dependence. Psychiatr Genet 9:69–73

    Article  PubMed  CAS  Google Scholar 

  • Sanger TD, Garg RR, Chen R (2001) Interactions between two different inhibitory systems in the human motor cortex. J Physiol 530.2:307–317

    Article  Google Scholar 

  • Siebner HR, Dressnandt J, Auer C, Conrad B (1998) Continuous intrathecal baclofen infusions induced a marked increase of the transcranially evoked silent period in a patient with generalized dystonia. Muscle Nerve 21:1209–1212

    Article  PubMed  CAS  Google Scholar 

  • Tergau F, Becher V, Canelo M, Wischer S, Wassermann EW, Ziemann U, Paulus W (1999) Complete suppression of voluntary motor drive during the silent period after transcranial magnetic stimulation. Exp Brain Res 124:447–454

    Article  PubMed  CAS  Google Scholar 

  • Tokimura H, Ridding MC, Tokimura Y, Amassian VE, Rothwell JC (1996) Short latency facilitation between pairs of threshold magnetic stimuli applied to human motor cortex. Electroencephalogr Clin Neurophysiol 101:263–272

    Article  PubMed  CAS  Google Scholar 

  • Valls-Sole J, Pascual-Leone A, Wassermann EM, Hallett M (1992) Human motor evoked responses to paired transcranial magnetic stimuli. Electroencephalogr Clin Neurophysiol 85:355–364

    Article  PubMed  CAS  Google Scholar 

  • Watanabe M, Maemura K, Kanbara K, Tamayama T, Hayasaki H (2002) GABA and GABA receptors in the central nervous system and other organs. Int Rev Cytol 213:1–47

    Article  PubMed  CAS  Google Scholar 

  • Werhahn KJ, Kunesch E, Noachtar S, Benecke R, Classen J (1999) Differential effects on motorcortical inhibition induced by blockade of GABA uptake in humans. J Physiol (Lond) 517:591–597

    Article  CAS  Google Scholar 

  • Ziemann U, Netz J, Szelenyi A, Hömberg V (1993) Spinal and supraspinal mechanisms contribute to the silent period in the contracting soleus muscle after transcranial magnetic stimulation of human motor cortex. Neurosci Lett 156:167–171

    Article  PubMed  CAS  Google Scholar 

  • Ziemann U, Lönnecker S, Steinhoff BJ, Paulus W (1996a) The effect of lorazepam on the motor cortical excitability in man. Exp Brain Res 109:127–135

    Article  CAS  Google Scholar 

  • Ziemann U, Lönnecker S, Steinhoff BJ, Paulus W (1996b) Effects of antiepileptic drugs on motor cortex excitability in humans: a transcranial magnetic stimulation study. Ann Neurol 40:367–378

    Article  CAS  Google Scholar 

  • Ziemann U, Rothwell JC, Ridding MC (1996c) Interaction between intracortical inhibition and facilitation in human motor cortex. J Physiol (Lond) 496:873–881

    CAS  Google Scholar 

  • Ziemann U, Tergau F, Wassermann EM, Wischer S, Hildebrandt J, Paulus W (1998) Demonstration of facilitatory I-wave interaction in the human motor cortex by paired transcranial magnetic stimulation. J Physiol (Lond) 511:181–190

    Article  CAS  Google Scholar 

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Acknowledgements

MM and YO were supported by fellowships awarded by the German Academic Exchange Service (DAAD).

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Correspondence to Ulf Ziemann.

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McDonnell, M.N., Orekhov, Y. & Ziemann, U. The role of GABAB receptors in intracortical inhibition in the human motor cortex. Exp Brain Res 173, 86–93 (2006). https://doi.org/10.1007/s00221-006-0365-2

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  • DOI: https://doi.org/10.1007/s00221-006-0365-2

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