Stress-induced changes in the analgesic and thermic effects of opioid peptides in the rat

Stress (e.g. restraint) potentiates analgesia and alters changes in body temperature induced by morphine administered either systemically or intracerebroventricularly (i.c.v.) in rats. In order to extend the generality of this phenomenon to opioid peptides, we determined whether the analgesic and thermic effects of i.c.v. D-Ala2-D-Leu5-enkephalin (DADLE) or D-Ala2-N-MePhe4-Gly5(ol)-enkephalin (DAGO), agonists selective for delta- and mu-opioid receptors, respectively, were affected by restraint stress. Analgesia was measured in the tail-flick test and core body temperature by rectal probe. The unstressed rats exhibited a dose-dependent increase in tail-flick latencies after administration of either DAGO or DADLE. Restrained rats treated with DAGO or DADLE had a greater analgesic response to each dose of peptide than did unstressed rats; both the magnitude and duration of the drug effect were increased. The unstressed group of rats responded to all doses of DAGO and DADLE with an increase of core temperature. In contrast, restrained rats showed a decrease of core temperature following injection with either DAGO or DADLE. Thus, restraint stress can significantly modify the effects of DAGO and DADLE on analgesia and body temperature in a manner that is qualitatively and quantitatively similar to that observed previously for morphine administered by the i.c.v. route.