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Neuroadaptation of rats to kappa agonists U-50,488 and tifluadom.

1. When U50 was given to rats over 5 d by twice-daily s.c. injection (but not when delivered by osmotic minipump), buprenorphine and naloxone each precipitated strong, qualitatively distinct, behavioral syndromes. 2. The same dose of buprenorphine provoked similar behaviors in rats given chronic U50 and chronic TIF (analogous s.c. injection protocols), suggestive of neuroadaptation to kappa agonists as a class. This adaptation clearly contrasts with that to chronic mu agonists. 3. The buprenorphine-induced syndrome was characterized by oral stereotypies which had an onset of about 5 min and a duration greater than 4 hr. The intensity was dependent on the dose of agonist injected. 4. The naloxone-induced syndrome was characterized by repetitive yawning and writhing. 5. If oral stereotypy, yawning and writhing are considered to represent an abstinence syndrome, then it will be necessary to use multiple or more selective kappa antagonists to fully unveil kappa dependence in the rat. 6. The present data indicate a strong trend toward the parallel development of tolerance in rats given a similar course of chronic U50 injections as those tested for physical dependence.