No evidence for a protracted change in endogenous opioid activity following chronic opiate treatment in mice: parallel recovery of cross tolerance to stress and morphine antinociception

The involvement of central endogenous opioids in swim-induced antinociception in mice is well documented. The response is attenuated by central or systemic naloxone, displays two-way cross tolerance with morphine and is correlated with apparent occupation of central opiate receptors by endogenous ligands. Swim-induced antinociception was utilised as an in vivo model of endogenous opioid function to investigate a possible protracted functional change in endogenous opioid release or inactivation following chronic opiate treatment. Antinociceptive responses (tailflick latency) to morphine (4.4 mg/kg, SC) and swimming were determined at various times following chronic methadone (24 days treatment, 102 mg/kg day in drinking water for the last 20 days) and chronic morphine (1 g/kg sustained release) treatment. In both experiments, parallel recovery from cross tolerance was observed for morphine-and swim-induced antinociception. These results were consistent with the view that no protracted functional change in the release or inactivation of endogenous opioids had occurred following chronic opiate treatment.