Differentiation of opiate receptors in the brain by the selective development of tolerance.

The selective development to either the delta-opiate receptor agonist D-Ala2,D-Leu5-enkephalin (DADL) or the mu-agonist sufentanyl (SUF) has been studied in the central nervous system of rats by use of osmotic minipumps for chronic administration of the drugs. The opiate-sensitive parameters analgesia and catatonia were investigated. Chronic intracerebroventricular infusion of DADL for 7 days produced a 15-fold shift in that for catatonia. In these rats, the potency of SUF in inducing analgesia and catatonia did not differ between DADL-treated animals and saline-infused controls. Similarly, chronic infusion of SUF resulted in tolerance towards SUF for both analgesia and catatonia. In these animals, DADL displayed a similar degree of tolerance w.r.t. its ability to evoke analgesia, whilst no tolerance could be detected for DADL-induced catatonia. The data indicate that prolonged stimulation of specific opiate receptors in the brain by selective agonists may bring about the selective development of tolerance for particular receptors. The data conflict with the notion that mu-receptors specifically mediate analgesia and delta-receptors catatonia.