PHACLOFEN-REVERSIBLE EFFECTS OF GABA IN THE SPINAL-CORD OF THE RAT

Our earlier observation that intrathecal administration of L- and D-baclofen had different effects on sympathetic output regulating arterial pressure and heart rate in the rat prompted the present study which was designed to determine whether intrathecal administration of GABA elicits a phaclofen-reversible effect on arterial pressure and/or heart rate and whether this effect mimics that of L-baclofen or that of D-baclofen. Following intrathecal administration of the GABA(A) antagonist, bicuculline (10 nmol), at the T9 level, administration of GABA at a dose of 5-mu-mol (n = 8) decreased arterial pressure and heart rate by about 25 mm Hg and 45 bpm, respectively. The responses started at 1-2 min and lasted 3-20 min: comparison was made with rats given NaCl (5-mu-mol, n = 5), which was without effect on arterial pressure and heart rate. In rats pretreated with both bicuculline and the GABA(B) antagonist, phaclofen (5-mu-mol intrathecally: n = 9), the effect of GABA on arterial pressure was attenuated and the effect of GABA on heart rate was absent; comparisons were made with rats given bicuculline, phaclofen and NaCl (n = 5) and with rats given bicuculline, NaCl and GABA (n = 6). These data suggest that there is a phaclofen-reversible effect of GABA in spinal pathways regulating sympathetic output and that this effect of GABA resembles that of L-baclofen reported in our earlier study. The persistence of an effect on arterial pressure of GABA in the presence of bicuculline and phaclofen at doses which block the effects of GABA on heart rate does not permit us to exclude the possibility that there may be a GABA effect on sympathetic output to the vessels which is mediated via a novel GABA-sensitive mechanism.