Sulfated cholecystokinin (26-33) induces mild taste aversion conditioning in rats when administered by three different routes.
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 (i.v.), intracerebroventricular (i.c.v.), or intraperitoneal (i.p.) administration. Significant TAC was induced by i.p. administration of CCK-8 at 0.1 but not at 0.025, 0.5, or 1.0 micromol/kg; the TAC was not robust and, in this case, not even dose related. I.p. administration of CCK-4 at 0.05, 0.1, 0.5, or 1.0 micromol/kg did not induce TAC, replicating other studies from our lab. Mild but significant TAC was also induced by i.v. administration of CCK-8 (at 0.025 and 1.0 but not 0.1 or 0.5 micromol/kg) but not by i.v. administration of CCK-4 (at 0.05, 0.1, 0.5, or 1.0 micromol/kg). Finally, mild but significant TAC was induced by i.c.v. (i.e., lateral ventricular) administration of CCK-8 (at 0.0015 but not at 0.015 micromol/brain) but not by i.c.v. administration of CCK-4 (at 0.005 or 0.010 micromol/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 i.c.v. or i.v. administrations of CCK-8 were not more efficacious than i.p. administration, the taste avoidance induced by i.p. 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 i.v. 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.
Mosher
J T
JT
Glaxo-Wellcome Research Institute, Research Triangle Park, NC 27709, USA.
Birkemo
L S
LS
Johnson
M F
MF
Ervin
G N
GN
D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D012844:Sincalide / Q000031:analogs & derivatives* / Q000494:pharmacology; D013463:Sulfuric Acid Esters / Q000494:pharmacology*; D013649:Taste / Q000502:physiology*
D013463:Sulfuric Acid Esters; C044201:cholecystokinin (26-33); D012844:Sincalide