An animal model for preclinical screening of systemic antipruritic agents

Reliable antipruritic agents that can be given systemically are not available at present. This may be due to the lack of animal models for screening such compounds. Bombesin, a tetradecapeptide originally isolated from frog skin, induces dose-related excessive scratching when administered intracerebroventricularly (i.c.v.) to rats. With the help of a microcomputer, we monitored the scratching elicited by a standard, submaximal dose of bombesin (0.10 microgram, i.c.v.). This system provides 1) a sensitive and novel way of assessing drug-induced behavioral depression, and 2) a means of quantifying interactions between bombesin and possible antagonists. Thus, bombesin-induced grooming is antagonized by behaviorally nondepressant doses of methdilazine, trimeprazine, and chlorpromazine but not by morphine, haloperidol, diphenhydramine, hydroxyzine, mepyramine, cimetidine, or cyproheptadine. Methdilazine and trimeprazine are used clinically as antipruritic agents. The model therefore offers a means of evaluating new, systemic antipruritic agents, particularly those which may be active in treating histamine-independent pruritus.