Leptin suppression of hypothalamic NPY expression and feeding, but not amygdala NPY expression and experimental anxiety.
Leptin decreases food intake through actions in the hypothalamus, partly through interactions with neuropeptide Y (NPY). However, NPY also produces behavioral antistress effects mediated inter alia through the amygdala. If leptin generally suppresses NPY function, the utility of leptin-mimics for treatment of obesity might be limited. Here, we therefore compared the effects of intracerebroventricular leptin on hypothalamic and amygdala NPY expression, as well as the respective related behaviors, i.e., feeding and experimental anxiety. Rats were injected intracerebroventricularly with leptin once daily for 6 days. Leptin-treated subjects consumed significantly less chow and had reduced body weight at the end of the treatment period compared to saline-treated controls. This was accompanied by a significant suppression of hypothalamic NPY expression. In contrast, the expression of NPY within the amygdala was unaffected by leptin. In parallel, in an established animal model of anxiety, the elevated plus-maze, no effect of leptin on anxiety-related behaviors was observed. In conclusion, leptin selectively affects the hypothalamic NPY system and its functional outflow, i.e., feeding and endocrine stress responses. Despite modifying endocrine responses, leptin treatment does not affect behavioral measures of experimental anxiety.
Thorsell
A
A
NEUROTEC, Karolinska Institutet, SE-141 86, Stockholm, Sweden. annika.thorsell@neurotec.ki.se
Caberlotto
L
L
Rimondini
R
R
Heilig
M
M
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000378:metabolism* / Q000517:prevention & control; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007276:Injections, Intraventricular; D020738:Leptin / Q000008:administration & dosage / Q000502:physiology*; D008297:Male; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D020738:Leptin; D009478:Neuropeptide Y; D012333:RNA, Messenger