Sulfated Cholecystokinin [26–33]Induces Mild Taste Aversion Conditioning in Rats when Administered by Three Different Routes

Abstract

We investigated the ability of sulfated cholecystokinin [26–33](CCK-8) and cholecystokinin [30–33](CCK-4) to induce taste aversion or avoidance conditioning (TAC) in a one-bottle testing paradigm after either intravenous (IV), intracerebroventricular (ICV), or intraperitoneal (IP) administration. Significant TAC was induced by IP administration of CCK-8 at 0.1 but not at 0.025, 0.5, or 1.0 μmol/kg; the TAC was not robust and, in this case, not even dose related. IP administration of CCK-4 at 0.05, 0.1, 0.5, or 1.0 μmol/kg did not induce TAC, replicating other studies from our lab. Mild but significant TAC was also induced by IV administration of CCK-8 (at 0.025 and 1.0 but not 0.1 or 0.5 μmol/kg) but not by IV administration of CCK-4 (at 0.05, 0.1, 0.5, or 1.0 μmol/kg). Finally, mild but significant TAC was induced by ICV (i.e., lateral ventricular) administration of CCK-8 (at 0.0015 but not at 0.015 μmol/brain) but not by ICV administration of CCK-4 (at 0.005 or 0.010 μmol/brain). Because CCK-4 failed to induce TAC, CCK-8 apparently induced TAC via all three routes by an action at a CCK A, not CCK B, receptor mechanism. Because ICV or IV administrations of CCK-8 were not more efficacious than IP administration, the taste avoidance induced by IP administration of CCK-8 was not so mild simply because it failed to reach a critical central locus adequately or because it failed to be delivered at a critical speed (i.e., via IV injections). We demonstrate that CCK-8 can induce mild TAC at either peripheral or central sites and suggest that these effects of CCK-8 may be independent and may be a sign of salience but not necessarily of toxicosis.