Behavioral effects of neuropeptide Y in F344 rat substrains with a reduced dipeptidyl-peptidase IV activity.
Dipeptidyl-peptidase IV (DPPIV/CD26) is involved in several physiological functions by cleavage of dipeptides with a Xaa-Pro or Xaa-Ala sequence of regulatory peptides such as neuropeptide Y (NPY). Cleavage of NPY by DPPIV results in NPY(3-36), which lacks affinity for the Y(1) but not for other NPY receptor subtypes. Among other effects, the NPY Y(1) receptor mediates anxiolytic-like effects of NPY. In previous studies with F344 rat substrains lacking endogenous DPPIV-like activity we found a reduced behavioral stress response, which might be due to a differential degradation of NPY. Here we tested this hypothesis and administered intracerebroventricularly two different doses of NPY (0.0, 0.2, 1.0 nmol) in mutant and wildtype-like F344 substrains. NPY dose-dependently stimulated food intake and feeding motivation, decreased motor activity in the plus maze and social interaction test, and exerted anxiolytic-like effects. More important for the present hypothesis, NPY administration was found to be more potent in the DPPIV-negative substrains in exerting anxiolytic-like effects (increased social interaction time in the social interaction test) and sedative-like effects (decreased motor activity in the elevated plus maze). These data demonstrate for the first time a differential potency of NPY in DPPIV-deficient rats and suggest a changed receptor-specificity of NPY, which may result from a differential degradation of NPY in this genetic model of DPPIV deficiency. Overall, these results provide direct evidence that NPY-mediated effects in the central nervous system are modulated by DPPIV-like enzymatic activity.
Karl
Tim
T
Department of Functional and Applied Anatomy, Hannover Medical School, Germany.
Hoffmann
Torsten
T
Pabst
Reinhard
R
von Hörsten
Stephan
S
D000818:Animals; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology; D007398:Interpersonal Relations; D009043:Motor Activity / Q000187:drug effects* / Q000235:genetics; D009478:Neuropeptide Y / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity
D009478:Neuropeptide Y; D018819:Dipeptidyl Peptidase 4