Local perfusion of mCPP into ventromedial hypothalamic nucleus, but not into lateral hypothalamic area and frontal cortex, inhibits food intake in rats.
BACKGROUND
The serotonergic (5-hydroxytryptamine, 5-HT) system is extensively implicated in feeding behavior. In recent years, 5-HT receptors have been classified into 14 subtypes, and activation of 5-HT1B and 5-HT2C receptors inhibits food intake in rats. However, the precise functions in local brain areas of these receptor subtypes are unclear.


OBJECTIVE
Frontal cortex (FC), lateral hypothalamic area (LH), or ventromedial hypothalamic nucleus (VMH) are involved in control of feeding behavior. We investigated the effects of 5-HT1B and 5-HT2C receptor stimulations in the three local brain areas on feeding behavior and on 5-HT metabolism.


METHODS
We perfused mCPP, 5-HT(1B/2C) agonist, at multiple doses via a microdialysis probe into the three local brain areas and observed food intake. Extracellular concentrations of 5-HT and 5-HIAA were measured simultaneously.


RESULTS
Perfusion of 1 mM mCPP into VMH, but not into LH nor FC at any dose, induced significant reduction of food intake compared with control. The extracellular concentrations of 5-HT were markedly increased in all three areas, but the concentrations of 5-HIAA were not changed by mCPP perfusions.


CONCLUSIONS
These results indicate that the effects of 5-HT1B or 5-HT2C receptor activation on feeding behaviors depended on the brain regions, and that 5-HT1B or 5-HT2C receptors in VMH, but not in FC or in LH, play important roles in the regulation of food intake. The results also suggested that mCPP acts not only as a 5-HT(1B/2C) agonist, but also as a 5-HT releaser or as a re-uptake inhibitor. Further studies using antagonists should be conducted.
Hikiji
Katsuhito
K
Department of Neuropsychiatry, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka City 545-8585, Osaka, Japan. hkatsujp@ybb.ne.jp
Inoue
Koki
K
Iwasaki
Shinichi
S
Ichihara
Kyuichiro
K
Kiriike
Nobuo
N
D000818:Animals; D005247:Feeding Behavior / Q000187:drug effects*; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D017551:Microdialysis; D010749:Phosphoprotein Phosphatases / Q000494:pharmacology*; D000071636:Protein Phosphatase 2C; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C