PHACLOFEN (cas 114012-12-3)-reversible effects of GABA in the spinal cord of the rat

Add time:08/27/2019    Source:sciencedirect.com

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 GABAA antagonist. bicuculline (10 nmol), at the T9 level, administration of GABA at a dose of 5 μmol (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 μmol; n = 5), which was without effect on arterial pressure and heart rate. In rats pretreated with both bicuculline and the GABAB antagonist, phaclofen (5 μmol 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 NaCI (n = 5) and with rats given bicuculline, NaCI and GABA (n = 6). These data suggest that there is a phaclofen-reverssible 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 GA3A 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.

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