Several roles of CCKA and CCKB receptor subtypes in CCK-8-induced and LiCl-induced taste aversion conditioning

Abstract Administration of a relatively large IP dose of sulfated cholecystokinin (26–33) (CCK-8; 1.0 μmol/kg) consistently induced moderate taste aversion conditioning (TAC) using a 20-min, one-bottle test in Long-Evans rats. Because CCK-8 has affinity for both CCK A and CCK B receptor subtypes, we wanted to determine the subtype involved in CCK-8-induced TAC. Pretreatment with the selective CCK A antagonist MK-329 (L-364,718 or devazepide), at doses of 0.1, 1.0, or 10.0 μmol/kg, markedly antagonized (> 70%) CCK-8-induced TAC. Pretreatment with the selective CCK B antagonist L-365,260, at doses of 0.1 or 1.0 μmol/kg, partially antagonized (∼50%) CCK-8-induced TAC, although the highest dose of L-365,260, 10.0 μmol/kg, did not. These partial antagonistic effects of L-365,260 on CCK-8-induced TAC were replicated in our second study. In our third study, we observed that another CCK B antagonist, the dipeptoid CI-988, also partially antagonized CCK-8-induced TAC at a dose of 0.1, but not 1.0 or 10.0, μmol/kg. In our final study, pretreatments with a single dose (i.e., 10.0, but not 0.1 or 1.0, μmol/kg) of either MK-329 or L-365,260 were also shown to partially antagonize the formation of moderate TAC induced by treatment with LiCl at 708 μmol/kg. Marked antagonism of LiCl-induced TAC was also observed following pretreatment with the known anxiolytic chlordiazepoxide HCl at 7.4 μmol/kg. Considering the existing data on the induction of TAC by various CCK analogues, we consider an action of CCK-8 on peripheral CCK A , but not CCK B , receptors necessary for the induction of TAC. Our results of partial antagonism of CCK-8- and LiCl-induced TAC by L-365,260, CI-988, or MK-329 suggest, but do not prove, that both CCK A and CCK B mechanisms may be operative during TAC. Because the CCK antagonists affected TAC like chlordiazepoxide, blockade of CCK A and CCK B mechanisms may produce a mild anxiolytic effect.