DIFFERENTIAL CROSS-TOLERANCE BETWEEN ANALGESIA PRODUCED BY ALPHA(2)-ADRENOCEPTOR AGONISTS AND RECEPTOR SUBTYPE-SELECTIVE OPIOID TREATMENTS

Analgesic cross-tolerance between alpha(2)-adrenoceptor and opioid receptor agonists was studied using the mouse tail-flick assay. Mice tolerant to clonidine (0.3 mg/kg s.c.) or xylazine (7 mg/kg s.c.) were cross-tolerant to morphine (5 mg/kg s.c.), nalorphine (70 mg/kg s.c.) and supraspinal [D-Ala(2),MePhe(4),Gly(ol)(5)]enkephalin (DAMGO; 4 ng i.c.v.), but not trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide methanesulfonate (U50,488; 5 mg/kg s.c.), spinal DAMGO (10 ng i.t.), supraspinal [D-Pen(2),D-Pen(5)]enkephalin (DPDPE; 9 mu g i.c.v.) or spinal DPDPE (700 ng i.t.). In the complimentary studies, mice tolerant to morphine and nalorphine were cross-tolerant to both of the alpha(2)-adrenoceptor agonists, but U50,488 tolerant mice were not. The results suggest differential interactions between alpha(2)-adrenoceptor and mu(1)-, mu(2)-, delta-, kappa(1)- and kappa(3)-opioid analgesic circuitry.