SEROTONERGIC Pontomedullary Neurons Are Not Activated by Antinociceptive Stimulation in the Periaqueductal Gray

The antinociceptive and cardiovascular effects of midbrain periaqueductal gray (PAG) stimulation are mediated through a relay in the pontomedullary raphe magnus (RM) and adjacent nucleus reticularis magnocellularis (NRMC). To test whether the neurons important in mediating PAG-evoked effects are SEROTONERGIC, the responses of pontomedullary SEROTONERGIC-LIKE cells to PAG stimulation were tested. SEROTONERGIC-LIKE neurons (n = 21) were recorded extracellularly in halothane-anesthetized Sprague Dawley rats. Serotonergic-like neurons were distinguished by their slow and steady background discharge. Two neurons that were physiologically characterized as SEROTONERGIC-LIKE were intracellularly labeled and processed for serotonin immunoreactivity; both cells tested contained immunoreactive serotonin. Train stimulation of sites within the midbrain PAG, at intensities of </=50 microA, suppressed the tail withdrawal from noxious heat and evoked changes in blood pressure and heart rate. No SEROTONERGIC-LIKE cells were activated by single-pulse or short-train (two to five pulses) stimulation of the PAG at antinociceptive intensities. In most cases, SEROTONERGIC-LIKE cells were unaffected by long-train stimulation (5-6 sec) of the PAG, which produced antinociception and cardiovascular changes. In contrast, >50% of the cells in two nonserotonergic-like cell classes were activated at short latency by such PAG stimulation. In conclusion, monosynaptic excitation of SEROTONERGIC cells in RM/NRMC is unlikely to be necessary for the nociceptive and autonomic modulatory effects of PAG stimulation.