Distribution and depression of the GABAB receptor in the spinal dorsal horn of adult rat

gamma -Aminobutyric acid (GABA) is a principal inhibitory neurotransmitter in vertebrate nervous system. The metabotropic receptor for GABA, GABA(B) receptor, is characterized as a G protein-coupled receptor subtype. In the present study, GABA(B) receptor-like immunoreactivity (GABA(B)R-LI) in the rat spinal cord and dorsal root ganglion (DRG), as well as GABA(B), receptor-mediated depression in the spinal dorsal horn were examined by using immunohistochemistry and whole-cell voltage-clamp recording technique, respectively. Under light microscope, GABA(B)R-LI was densely found in laminae I and II of the dorsal horn. DRG cells of various diameters also showed GABA(B)R-LI. Electron microscopy further revealed that GABA(B)R-LI was also localized in terminals of myelinated, unmyelinated fibers as well as the somatodendritic sites of dorsal horn neurons. Bath application of a GABA(B) receptor agonist, baclofen (10 muM, 30 s), induced a slow outward (inhibitory) current in dorsal horn neurons. This slow current was depressed when the postsynaptic G protein-coupled receptor was inhibited, indicating the postsynaptic action of baclofen. Under the condition of postsynaptic GABA(B) receptor being inhibited, baclofen (10 muM, 60 s) depressed large (A beta) and fine (C, A delta) afferent fiber-evoked monosynaptic excitatory postsynaptic currents, indicating presynaptic inhibition of GABA(B), receptor on elicited neurotransmitter release. Taken together, the results suggest that baclofen-sensitive GABA(B) receptor is expressed pre- and postsynaptically on primary afferent fibers and neurons in the spinal dorsal horn; activation of GABA(B) receptor in the dorsal horn postsynaptically hyperpolarizes dorsal horn neurons and presynaptically inhibits primary afferents. (C) 2001 Elsevier Science Inc.