Are baclofen-sensitive GABAB receptors present on primary afferent terminals of the spinal cord?

Abstract

The site of action of the antispastic drug baclofen has long been considered to reside in the spinal cord1,2 although supraspinal effects have also been reported3–6. This β-chlorophenyl derivative of the neurotransmitter γ-aminobutyric acid (GABA) depresses both monosynaptic and polysynaptic transmission in the cord7 possibly through a decrease in transmitter release rather than by any antagonism at postsynaptic receptors7–10. Recently, baclofen has been shown to be a selective ligand for a bicuculline-insensitive GABA receptor (GABAB) site11,12 that occurs widely in the mammalian central nervous system including the spinal cord13. The apparent importance of the cord in the therapeutic effects of this drug prompted us to ask whether they involve GABAB site activation. As an initial step we have located these receptors by autoradiography, comparing them with classical GABAA sites. We report here that GABAB sites, unlike GABAA sites, are present in high concentrations in laminae I, II, III and IV of the dorsal horn and that after the neonatal administration of capsaicin this binding is reduced by 40–50%.