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Thresholds to noxious heat stimulation were increased following microinjection of zimelidine, an inhibitor of 5-hydroxytryptamine (5-HT) re-uptake, into the nucleus raphe magnus (NRM) of rats. Pretreatment with intraperitoneally given cinanserin reduced this effect but pretreatment with intraperitoneally given phenoxybenzamine did not. Fenfluramine, which causes the release of 5-HT from synaptic terminals also elevated nociceptive thresholds following microinjection into NRM. Subanalgesic doses of morphine or zimelidine elevated nociceptive thresholds when microinjected together into NRM. The elevation of nociceptive threshold produced by microinjection of morphine into NRM was reduced by simultaneous microinjection of cinanserin into NRM. Cinanserin alone had no effect when microinjected into NRM. These findings suggest that inhibition of the re-uptake of 5-HT in NRM can elevate nociceptive thresholds and that there may be an interaction between the effects of morphine and 5-HT in NRM.
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