Release of endogenous monoamines into spinal cord superfusates following the microinjection of phentolamine into the nucleus raphe magnus.

Previous studies have suggested that raphe-spinal neurons located in the nucleus raphe magnus (NRM) are tonically inhibited by noradrenergic neurons. Furthermore, blockade of the inhibitory noradrenergic input to the NRM induces antinociception which appears to be mediated by the release of both serotonin and norepinephrine in the spinal cord. The present experiments were designed to directly measure the release of endogenous serotonin and norepinephrine into spinal cord superfusates before and after the microinjection of the alpha-adrenergic antagonist phentolamine into the NRM. High-performance liquid chromatography with electrochemical detection was used to quantitate the monoamines. The injection of phentolamine into the NRM induced a significant increase in the amount of both norepinephrine and serotonin released in the spinal cord. This enhanced release was not observed following either the injection of phentolamine into sites outside the NRM or the injection of saline vehicle into the NRM. These results support the proposal that the antinociception induced by the blockade of the inhibitory noradrenergic input to the NRM is mediated by the activation of spinally-projecting serotonergic and noradrenergic neurons.