Several studies indicate that central serotonergic neurons have important role in morphine analgesia and tolerance. The aim of this study was to investigate possible role of 5-HT(1A) and 5-HT(2) receptors in dorsal and median raphe nucleus on development of tolerance to analgesic effect of morphine using hot plate test. Chronic injection of 5-HT(1A) receptor agonist 8-OH-DPAT (8-hydroxy-2-[di-n-propylamino]tetralin) (2, 4 and 8 mug/rat/day) to dorsal raphe nucleus (DRN) delayed tolerance to morphine analgesia, whereas injection of the same doses of 8-OH-DPAT to the median raphe nucleus (MRN) did not alter tolerance to morphine. In addition, chronic administration of ketanserin (1.5, 3 and 6 mug/rat/day), as a 5-HT(2) receptors antagonist, in DRN and MRN did not produce any significant effect. We conclude that 5-HT(1A) receptors of DRN are involved in tolerance to antinociceptive effect of morphine. However, the exact mechanism of interaction between serotonergic and opioidergic systems is not clear and remains to be elucidated.
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