Tolerance and physical dependence induced by dermorphin in rats

Rats chronically implanted with osmotic minipumps in the left lateral ventricle were used to study the ability of dermorphin to produce tolerance and physical dependence. The development of tolerance, assessed by evaluating the time reduction of analgesia, catalepsy and rigidity, occurred in a dose-dependent fashion over a maximum period of 48 h. After 3 days of peptide infusions into the rat brain, the dependent state was established and was revealed by precipitating the withdrawal syndrome with intraperitoneal naloxone injections. Escape behavior, shaking, salivation and rhynorrhea were the main symptoms, qualitatively similar to those obtained in rats made dependent on morphine. Considering that dermorphin displays strong analgesic activity, the well-known combination of antinociception tolerance and dependence capacities of opiates also seems to be valid for dermorphin.