Cross-tolerance between dermorphin and morphine to analgesia and catalepsy in rats

Rats were made tolerant to dermorphin or to morphine by continuous ICV infusion of these drugs. Tolerance to the analgesic effect was assessed by evaluating the shift of the ED50 of dermorphin or morphine in dermorphin-infused or in morphine-infused animal respectively, after single doses of these opioids. Tolerance to catalepsy was revealed with the significant reduction of this effect after single ICV dose of morphine in morphine-infused and dermorphin in dermorphin-infused rats. Both dermorphin and morphine induced tolerance to the analgesic and cataleptic effects. Acute administration (SC and ICV) of morphine in DER-tolerant rats induced a significant decrease of the analgesic and cataleptic effects of this opioid, showing the onset of cross-tolerance between morphine and dermorphin. Acute injections of dermorphin (ICV) in MOR-tolerant rats, while significantly decreasing its analgesic potency, indicating the development of cross-tolerance, did not modify the cataleptic response to the peptide, showing that no cross-tolerance was present to this effect.