Role of opioid receptors in bombesin-induced grooming.

Bombesin, a tetradecapeptide originally isolated from the skin of the frog Bombina bombina,’ elicits dose-related excessive grooming when injected centrally in rats2-‘ as well as other specie^.^ The grooming induced by intracerebroventricular (i.cv.) bombesin in rats consists of hindlimb scratching directed primarily at the head and neck, although facial grooming, body washing, nail licking and biting, forepaw tremors, wetdog shakes, and stretching also occur. Bombesin-induced grooming behavior can be observed within a few minutes of i.c.v. injection and continues for 30-45 minutes. In contrast to the grooming induced by a variety of other peptides such as ACTHI-,,, thyrotropin-releasing hormone, substance P, P-endorphin, and nonpeptides such as RX 336-M (7,8-dihydro-5’,6‘-dimethylcyclohex-5’-en0-1’,2~,8~,14 codeinone), bombesininduced grooming is not inhibited by nonsedative doses of In keeping with multiple types of cholinergic, adrenergic, histaminic, and dopaminergic receptors, it is also well established that there are multiple types of opioid receptors. Based on observations in dogs, the existence of three types of opioid receptors was postulated: mu (for which morphine was the prototype), kappa (for which ketocyclazocine was the prototype) and sigma (for which N-allyl-normetazocine was the prototype).l2.l3 Since then, mu and kappa types of opioid receptors have been differentiated by biochemical studies using receptor binding and visualization techniques (see, for example, refs. 14 and 15) and by pharmacological studies in which differences in acute effects, differences in the ease of antagonism by the opioid-specific antagonist naloxone, and the selective development of tolerance and dependence were identified (see refs. 16-18). Whereas sigma receptors are no longer considered to be opioid (i.e., naloxone is not an antagonist of effects mediated by the “sigma” receptor), a third type of opioid receptor has been identified primarily through in vitro studies, the delta re~eptor.’~ The endogenous enkephalins have been proposed as natural ligands for the delta receptor. In light of the multiple classes of opioids, we decided to examine opioids other than morphine for their ability to inhibit bombesin-induced grooming in rats. In our