The Pharmacology and Function of Central GabaB Receptors

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This chapter focuses on the pharmacological properties of GABAB receptors, the intracellular signaling systems to which these receptors are coupled, and their role in regulating synaptic transmission in the central nervous system. GABAB receptors enable GABA to modulate neuronal function in a manner not possible through GABAB receptors alone. These receptors are present at both pre- and postsynaptic sites and can exert both inhibitory and disinhibitory effects. In particular, GABAB receptors are important in regulating NMDA receptor-mediated responses, including the induction of long-term potentiation (LTP). They also can regulate the filtering properties of neural networks, allowing peak transmission in the frequency range of theta rhythm. GABAB receptors are G protein-coupled to a variety of intracellular effector systems, and thereby, have the potential to produce long-term changes in the state of neuronal activity, through actions such as protein phosphorylation. Although the majority of the effects of GABAB receptors have been reported in vitro, recent studies demonstrate that GABAB receptors exert electrophysiological actions in vivo. For example, GABAB receptor antagonists reduce the late inhibitory postsynaptic potential (IPSP) in vivo and consequently, can decrease inhibition of spontaneous neuronal firing following a stimulus. In addition, blockade of GABAB receptors can increase spontaneous activity of central neurons, suggesting the presence of GABAB receptor-mediated tonic inhibition.

References (491)

  • M.I. Al-Dahan et al.

    Brain Res.

    (1990)
  • D.G. Amaral

    Curr. Opin. Neurobiol.

    (1993)
  • R.A. Anderson et al.

    Eur. J. Pharmacol.

    (1985)
  • R. Andrade

    Eur. J. Pharmacol.

    (1991)
  • R. Andrade

    Neuron

    (1993)
  • P. Andre et al.

    Eur. J. Pharmacol.

    (1992)
  • R. Anwyl

    Brain Res.

    (1991)
  • T. Asano et al.

    Eur. J. Pharmacol.

    (1982)
  • T. Asano et al.

    J. Biol. Chem.

    (1985)
  • T.J. Ashwood et al.

    Brain Res.

    (1984)
  • K. Beaumont et al.

    Brain Res.

    (1978)
  • T.J. Blaxter et al.

    Brain Res.

    (1985)
  • G. Bonanno et al.

    Eur. J. Pharmacol.

    (1989)
  • J. Bormann

    Trends. Neurosci.

    (1988)
  • H.R. Bourne et al.

    Neuron

    (1993)
  • N.G. Bowery

    Trends Pharmacol. Sci.

    (1989)
  • N.G. Bowery et al.

    Neuropharmacology

    (1985)
  • N.G. Bowery et al.

    Neuroscience (Oxford)

    (1987)
  • F.H. Brucato et al.

    Brain Res.

    (1992)
  • G. Buzsáki

    Neuroscience (Oxford)

    (1989)
  • C.R. Cain et al.

    Neuropharmacology

    (1982)
  • P. Calabresi et al.

    Neurosci. Lett.

    (1990)
  • E. Carbone et al.

    Prog. Biophys. Mol. Biol.

    (1989)
  • N.L. Chamberlin et al.

    Brain Res.

    (1989)
  • D.C.M. Chu et al.

    Neuroscience (Oxford)

    (1990)
  • G.G.S. Collins et al.

    Brain Res.

    (1982)
  • W.F. Colmers et al.

    Neurosci. Lett.

    (1988)
  • V. Crunelli et al.

    Trends Neurosci.

    (1991)
  • D.R. Curtis et al.

    Brain Res.

    (1974)
  • D.R. Curtis et al.

    Neurosci. Lett.

    (1988)
  • M.I. Al-Dahan et al.

    J. Neurochem.

    (1989)
  • S. Alford et al.

    J. Neurosci.

    (1991)
  • B.E. Alger

    J. Neurophysiol.

    (1984)
  • B.E. Alger

    Ann. N.Y. Acad. Sci.

    (1991)
  • B.E. Alger et al.

    Science

    (1980)
  • B.E. Alger et al.

    J. Physiol. (London)

    (1982)
  • B.E. Alger et al.

    J. Physiol. (London)

    (1982)
  • C.A. Allerton et al.

    Br. J. Pharmacol.

    (1989)
  • G. Alvarex de Toledo et al.

    J. Physiol. (London)

    (1988)
  • D.G. Amaral

    J. Comp. Neurol.

    (1978)
  • P. Andersen et al.

    Nature (London)

    (1963)
  • R. Andrade et al.

    Science

    (1986)
  • M.H. Aprison et al.

    J. Neurosci. Res.

    (1989)
  • E.K. Asprodini et al.

    J. Pharmacol. Exp. Ther.

    (1992)
  • G.J. Augustine et al.

    Annu. Rev. Neurosci.

    (1987)
  • B. Ault et al.

    J. Pharmacol. Exp. Ther.

    (1982)
  • B. Ault et al.

    Br. J. Pharmacol.

    (1983)
  • B. Ault et al.

    Br. J. Pharmacol.

    (1983)
  • T.L. Babb et al.

    J. Comp. Neurol.

    (1988)
  • B.A. Ballyk et al.

    J. Neurosci. Res.

    (1992)
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      CSP is mediated by both ionotropic GABAA and the metabotropic GABAB receptors (Mott and Lewis, 1994; Rossini et al., 2015) as well as by glutamatergic activity (Tremblay et al., 2013; Dyke et al., 2017). Increased activity of both GABAA and GABAB suppresses neuronal depolarization and undermines LTP formation (Mott and Lewis, 1994; Jurado-Parras et al., 2016). Accordingly, in healthy individuals, less GABAergic inhibition measured as shorter CSP predicts enhanced LTP response (Sale et al., 2007) assessed with paired-associative stimulation (Meunier et al., 2007).

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