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.