Clonidine sensitizes mice for apomorphine-induced stereotypic gnawing: antagonism by neuroleptics and cholecystokinin-like peptides.

In mice sensitized for apomorphine by either scopolamine or teflutixol, clonidine antagonized the antistereotypic effect of ceruletide and haloperidol. The same effect of clonidine occurred in normal mice with methylphenidate-induced gnawing. In naive mice, clonidine alone had a sensitizing effect for the action of apomorphine leading to wire-gnawing. Yohimbine and rauwolscine (but not corynanthine) antagonized this effect of clonidine. The gnawing-inducing effect of methylphenidate was also enhanced by clonidine but not to the same extent as that of apomorphine. The stereotypic effect of apomorphine (in mice sensitized by either scopolamine or clonidine) was antagonized by yohimbine and rauwolscine but not by corynanthine. Apomorphine-induced wire gnawing was used as test of the antistereotypic effect of haloperidol, trifluoperazine, teflutixol, CCK-8, ceruletide and 8 related peptides. Ceruletide and 2 of its analogues were more potent than the neuroleptics; CCK-8 was 7 times less active than ceruletide. In conclusion, clonidine sensitized mice for the stereotypic effect (wire-gnawing) of apomorphine and methylphenidate. The clonidine-apomorphine effect permits the estimation of antistereotypic effects.