MULTIPLE, SMALL DOSES OF CHOLECYSTOKININ-OCTAPEPTIDE ARE MORE EFFICACIOUS AT INDUCING TASTE-AVERSION CONDITIONING THAN SINGLE, LARGE DOSES

Using a one-bottle taste aversion conditioning paradigm, sulfated cholecystokinin(26-33) (CCK-8) has again been shown to induce taste aversion conditioning in rats. Even thought the effective doses of CCK-8 are relatively high, they do not induce as strong an aversion as has been demonstrated with LiCl. This pharmacodynamic profile of CCK-8 (i.e., relatively moderate, but not strong, taste aversion induction) may result, in part, from its unusual pharmacokinetic profile. CCK-8 seems to have a plasma half-life of just several minutes, whereas LiCl has a plasma half-life of 6 h in rats. In the present study, CCK-8, CCK-4, or LiCl was administered either as single, large doses immediately following consumption of 0.2% sodium saccharin (SACC), or as 10 half-hourly injections of one-tenth the large dose. Presumably, multiple small doses extended the time CCK-8 and CCK-4 were acting in the body, even though the peak plasma concentrations were quantitatively lower than after the large, single doses. Ten injections of CCK-8 of 10 or 100 nmol/kg (11.4 or 114.3 μg/kg) induced significantly stronger taste aversions than single injections of the same total dose of 100 or 1000 nmol/kg (114.3 or 1143.3 μg/kg), whereas multiple injections of LiCl of 70.8 μmol/kg (3.0 mg/kg × 10) did not induce stronger taste aversions than single injections of 708 μmol/kg (30.0 mg/kg). Neither single nor multiple injections of CCK-4 of 1000 nmol/kg (596.7 μg/kg) × 1, or 100 or 1000 nmol/kg (59.7 or 596.7 μg/kg) × 10 induced any sign of taste aversion conditioning. Therefore, CCK-8-induced taste aversions appear so mild, in part, because of CCK-8's unusually brief pharmacokinetic profile. © 1995.