(-)-Baclofen activates presynaptic GABAB receptors on GABAergic inhibitory neurons from embryonic rat hippocampus.
GABA-mediated monosynaptic inhibitory postsynaptic currents were recorded at synapses between embryonic rat hippocampal neurons in culture. The GABAB receptor agonist L(-)-baclofen reduced inhibitory postsynaptic current amplitude substantially at 10 microM, while the D(+)-isomer of baclofen was without effect. L(-)-Baclofen did not increase postsynaptic membrane conductance or block postsynaptic membrane responses to GABA. It is concluded that L(-)-baclofen depresses GABA-mediated inhibitory postsynaptic potentials by a presynaptic action at GABAB receptors on or near the terminals of the inhibitory neuron. The possible physiological importance of these presynaptic 'autoreceptors' is discussed.
Harrison
N L
NL
Laboratory of Neurophysiology, National Institute for Neurological and Communicative Disorders and Stroke, Bethesda, MD 20892.
Lange
G D
GD
Barker
J L
JL
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D002478:Cells, Cultured; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects / Q000196:embryology / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology
D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D001418:Baclofen