Systemic Administration of (Tyr.-D-Ser(O-Tert-Butyl)-GIy-Phe-- Leu-Thr(O-Tert-Butyl), a Highly Selective Delta Opioid Agonist, Induces Mu Receptor-Mediated Analgesia in Mice

The mu opioid receptors are unquestionably implicated both in supraspinal and spinal analgesia, but there is some controversy about the role of delta receptors in the control of pain at the supraspinal level. This could be due, at least in part, to the local or i.c.v. administration of the opioid agonists. It was therefore interesting to reassess the overall contribution of mu and delta opioid receptors in modulating nociceptive thermal stimuli in the hot plate-test in mice after i.v. injections of DAMGO (Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol) and BUBU (Tyr-D-Ser(O-tert-butyl)-Gly-Phe-Leu-Thr(O-tert-butyl), two highly selective mu and delta receptor agonists, respectively, whose passage into the brain has been demonstrated recently. Both agonists induced dose-dependent, short-lasting (<30 mm), antinociceptive responses that peaked 5 mm after the administration of DAMGO and 1