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 though 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 micrograms/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 micrograms/kg), whereas multiple injections of LiCl of 70.8 mumol/kg (3.0 mg/kg x 10) did not induce stronger taste aversions than single injections of 708 mumol/kg (30.0 mg/kg). Neither single nor multiple injections of CCK-4 of 1000 nmol/kg (596.7 micrograms/kg) x 1, or 100 or 1000 nmol/kg (59.7 or 596.7 micrograms/kg) x 10 induced any sign of taste aversion conditioning.(ABSTRACT TRUNCATED AT 250 WORDS)
Ervin
G N
GN
Glaxo Research Institute, Research Triangle Park, NC 27709, USA.
Mosher
J T
JT
Birkemo
L S
LS
Johnson
M F
MF
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D018021:Lithium Chloride / Q000008:administration & dosage; D008297:Male; D051381:Rats; D012844:Sincalide / Q000008:administration & dosage*; D013223:Statistics as Topic; D013649:Taste / Q000187:drug effects*; D013758:Tetragastrin / Q000008:administration & dosage*
D013758:Tetragastrin; D018021:Lithium Chloride; D012844:Sincalide