Inhibitory effect of baclofen on GABA-induced depolarization and GABA-activated current in primary sensory neurons

Neuroscience. 1997 Dec;81(3):821-7. doi: 10.1016/s0306-4522(97)00107-3.

Abstract

It has been established that GABAA and GABAB receptors can exist separately and/or co-exist in the membrane of dorsal root ganglion neurons. In our previous investigation it has been shown that co-existence of these two kinds of receptors is about 80% of the neurons examined (20/25). The present study was aimed to explore whether the activation of these two kinds of receptors could interact with each other using intracellular and whole-cell patch-clamp recordings. Baclofen, a specific GABAB receptor agonist, was found to exert negative modulatory effects on the responses mediated by GABAA receptor. In experiments with intracellular recording, GABA (0.3-1000 microM)- and muscimol (100-1000 microM)-induced depolarization was attenuated markedly and reversibly by preapplication of baclofen (100 microM) (15/21 and 17/21, respectively). In whole-cell patch-clamp recordings GABA (100 microM) and two specific GABAA receptor agonists, muscimol (10 microM) and isoguvacine (50 microM), activated currents were inhibited markedly by preapplication of baclofen 30 s or more and the inhibition was concentration dependent (1-100 microM baclofen) and reversible. The possible mechanisms underlying the inhibition by baclofen of the responses mediated by GABAA receptor and the physiological significance implicated are discussed.

MeSH terms

  • Animals
  • Baclofen / pharmacology*
  • Electric Conductivity
  • Electrophysiology
  • Female
  • GABA Agonists / pharmacology*
  • Isonicotinic Acids / pharmacology
  • Male
  • Muscimol / pharmacology
  • Neurons, Afferent / drug effects*
  • Neurons, Afferent / physiology*
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • gamma-Aminobutyric Acid / pharmacology*

Substances

  • GABA Agonists
  • Isonicotinic Acids
  • Muscimol
  • gamma-Aminobutyric Acid
  • Baclofen
  • isoguvacine