GABA-B RECEPTOR-MEDIATED INHIBITION OF FORSKOLIN-STIMULATED CYCLIC-AMP ACCUMULATION IN RAT SPINAL-CORD

GABA (30-1000 muM) and the GABA(B) agonist, (-)baclofen (10-100 muM), but not (+)baclofen, inhibited forskolin-induced cAMP formation in rat spinal cord slices. In contrast, GABA and (-)baclofen failed to enhance the stimulation of cAMP induced by noradrenaline in the same tissue, even though they both increased the response to noradrenaline in cerebral cortex slices. Neonatal capsaicin treatment, which reduces the density of GABA(B) binding sites in the cord, did not modify the effect of GABA or (-)baclofen on the forskolin-induced elevation of cAMP. (-)Baclofen and GABA inhibition of forskolin effects were insensitive to the GABA(B) antagonists CGP 35348 and CGP 36742 in the spinal cord. Since CGP 35348 antagonizes baclofen-induced antinociception, it seems unlikely that this effect stems from any change in cAMP within the spinal cord.