SUPRASPINAL DELTA(1)-OPIOID RECEPTOR-MEDIATED ANTINOCICEPTIVE PROPERTIES OF (-)-TAN-67 IN DIABETIC MICE

The antinociceptive potencies of the enantiomorphs of TAN-67 (2-methyl -4a alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12a alpha-octahydroquinoli no[2,3,3,-g]isoquinoline), (-)-TAN-67 and(+)-TAN-67, given intracerebr oventricularly (i.c.v.) on the antinociceptive response were studied i n streptozotocin-induced diabetic mice using the tail-flick test. (-)- TAN-67 at doses of 3-10 mu g given i.c.v. produced dose-dependent inhi bition of the tail-flick response in both non-diabetic and diabetic mi ce. The antinociceptive effect of (-)-TAN-67 in the tail-flick test in diabetic mice was greater than that in non-diabetic mice. The antinoc iceptive effect of (-)-TAN-67 was not antagonized by pretreatment with either beta-funaltrexamine, a selective mu-opioid receptor antagonist , or nor-binaltorphimine, a selective K-opioid receptor antagonist. Wh en 7-benzylidenenaltrexone, a selective delta(1)-opioid receptor antag onist, was administered 10 min before treatment with (-)-TAN-67, the a ntinociceptive effect of(-)-TAN-67 was significantly antagonized. Howe ver, naltriben, a selective delta(2)-opioid receptor antagonist, had n o significant effect on the antinociceptive effect cf (-)-TAN-67. On t he other hand, in the tail-flick test, (+)-TAN-67 at doses of 3-30 mu g given i.c.v. did not produce dose-dependent inhibition of the tail-f lick response in either non-diabetic or diabetic mice. In conclusion, (-)-TAN-67, but not its enantiomer (+)-TAN-67, produced an antinocicep tive effect through the activation of delta(1)-opioid receptors. (C) 1 997 Elsevier Science B.V.