The effects of bilateral intranigral microinjection of selective opioid agonists on behavioral responses to noxious thermal stimuli.

This study examined the effects of bilateral intranigral microinjection of selective opioid agonists on the tail-flick and hot-plate antinociception tests. The principal findings are: (1) the mu-selective agonist D-Ala2, N-Me-Phe4, Gly5-ol-enkephalin (DAGO) had antinociceptive effects on both tests which were reversible by beta-funaltrexamine (beta-FNA: a mu-selective antagonist) and naloxone (a non-selective opioid antagonist); (2) the antinociceptive potency of DAGO injected into the nigra is comparable to its potency in the periaqueductal gray; (3) intranigral D-Pen2, D-Pen5-enkephalin (a delta-selective agonist), U-50, 488H and dynorphin A-(1-13) (kappa-selective agonists) had no antinociceptive effects; (4) antinociceptive effects were produced by the mixed delta/mu agonists D-Thr2-leucine enkephalin-Thr (DTLET) and D-Ser2-leucine enkephalin-Thr (DSLET); (5) the effect of DTLET on the hot-plate but not the tail-flick test was reversed by Cys2, Tyr3, Orn5, Pen7-amide (CTOP; a mu-selective antagonist), beta-FNA, and naloxone, but not by the delta-selective antagonist naltrindole. Based on the potent antinociceptive effects of DAGO, the complete lack of such effects by the highly selective delta and kappa agonists, and the antagonism of DTLET by CTOP and beta-FNA, it is concluded that the antinociceptive effects of intranigral opioid agonists are mediated by mu receptors.