In vivo evidence for benzomorphan-selective receptors in rats.

The scratching caused by a standard, submaximal dose of bombesin (0.10 microgram i.c.v.) in rats is antagonized in a stereospecific and dose-related manner by systemically (but not centrally) administered benzomorphan analgesics; other commonly used opioids and opioid peptides are ineffective at behaviorally nondepressent doses. Naloxone attenuates the antibombesin effect of ethylketocyclazocine in a stereospecific, potent and dose-related manner. Tolerance develops to the inhibitory action of ethylketocyclazocine (and phenazocine). Multiple injections of morphine do not influence the ability of ethylketocyclazocine or of phenazocine to antagonize bombesin. Furthermore, when mu opiate receptors are occluded by buprenorphine, ethylketocyclazocine and phenazocine can still antagonize bombesin-induced scratching. Benzomorphan-selective binding sites have previously been postulated; we suggest that this test provides evidence of such sites in vivo. The model affords a simple, yet novel, behavioral endpoint that can be used when defining the pharmacological profile of new benzomorphans and their antagonists.