The effect of alpha(2)-adrenergic drugs on the activity of neurons in the rat nucleus raphe magnus in vitro

The nucleus raphe magnus (NRM) is an important descending inhibitory system for pain transmission. We tested whether clonidine, an alpha(2)-adrenergic agonist, and yohimbine, an alpha(2)-adrenergic antagonist, modulate the ac tivity of NRM neurons using extracellular recording in a rat brainstem slic e preparation. Clonidine 1-20 mu M increased firing frequencies (FF) in 22 (37%) and decreased FF in 6 (10%) spontaneously active neurons. Correlation between the concentrations of clonidine and FF changes was unremarkable. E ight spontaneously active neurons (13%) showed increases followed by decrea ses in FF with increasing doses of clonidine. The remaining 24 neurons (40% ) showed no change in FF. Yohimbine 1 mu M decreased FF in 38 spontaneously active neurons (58%), whereas the remaining 27 neurons (42%) showed no cha nge in FF. In some neurons, yohimbine antagonized the increase or decrease in FF by application of clonidine. In three silent neurons (25%), clonidine (5 or 10 mu M) induced firing activity, which stopped or decreased with th e increasing doses of clonidine. In the remaining nine neurons (75%), cloni dine did not induce firing activity. We conclude that activation and inhibi tion of alpha(2)-adrenergic receptors of NRM neurons augments and suppresse s output of the descending inhibitory pain pathway. Implications: The nucle us raphe magnus is implicated in descending control of the nociceptive proc esses. We found that clonidine and yohimbine increased and decreased, respe ctively, the firing activity of a substantial number of nucleus raphe magnu s neurons. Clonidine and may facilitate and yohimbine may reduce the outflo w of the descending inhibitory pathway.