Effects of the novel cholecystokinin analogue Suc-Trp-N(Me)-Nle-Asp-Phe-NH2 on feeding and cortisol release in pigs.
Suc-Try-N-(Me)-Nle-Asp-Phe-NH2 is a succinylated tetrapeptide derived from the C-terminal sequence of cholecystokinin octapeptide (CCK-B), which has been shown to have high agonist affinity for CCKB receptors. To test the validity of the hypothesis that implicates central CCKB receptors in the aetiology of stress-related disorders, such as anxiety and panic, we argued that activation of these receptors by a CCKB receptor agonist should (i) suppress feeding motivation in hungry animals and (ii) increase plasma concentrations of the stress hormone cortisol. The effects of systemic and central administration of Suc-Try-N-(Me)-Nle-Asp-Phe-NH2 were, therefore, investigated on operant food intake and cortisol secretion in pigs. Intravenous administration of Suc-Try-N-(Me)-Nle-Asp-Phe-NH2 (0.5-5 micrograms/kg) did not affect operant feeding in food-deprived pigs, although the highest dose (5 micrograms/kg) produced a small but significant (p < 0.05) increase in plasma cortisol levels 5-30 min after injection. Intracerebroventricular injection of Suc-Try-N-(Me)-Nle-Asp- Phe-NH2 (1-5 micrograms) had no effect on operant feeding and cortisol secretion in this species. The results obtained in this study indicate that central CCKB receptors are unlikely to be involved in stress-related behaviours in pigs.
Ebenezer
I S
IS
Neuropharmacology Research Group, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Hampshire, UK. ebenezeri@sci1.sci.port.ac.uk
Parrott
R F
RF
Goode
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D002766:Cholecystokinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D005502:Food; D006854:Hydrocortisone / Q000378:metabolism*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D012054:Reinforcement, Psychology; D013552:Swine
D009842:Oligopeptides; C098248:succinyl-tryptophyl-N-methyl-norleucyl-aspartyl-phenylalaninamide; D002766:Cholecystokinin; D006854:Hydrocortisone