4.6 Article

Dopaminergic mechanisms in the lateral hypothalamus regulate feeding behavior in association with neuropeptides

Journal

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2019.09.037

Keywords

Food intake; Hypothalamus; Dopamine neuron; Feeding-related peptide; Mice

Funding

  1. JSPS KAKENHI [26430024]
  2. Invitation Fellowship for Research in Japan [S16093]
  3. Hoshi University Ohtani Research Grants
  4. Grants-in-Aid for Scientific Research [26430024] Funding Source: KAKEN

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This study investigated dopaminergic function in the lateral hypothalamus (LH) in the regulation of feeding behavior. Refeeding increased dopamine levels in the LH. Glucose injection also increased dopamine levels in the LH. When the retrograde tracer Fluoro-Gold (FG) was injected into the LH, FG-positive cells were found in the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNC), which were mostly tyrosine hydroxylase-positive. Injection of the dopamine D-1 receptor agonist SKF 38393, but not the antagonist SCH 23390, into the LH increased food intake. Similarly, injection of the dopamine D-2 receptor agonist quinpirole, but not the antagonist I-sulpiride, into the LH increased food intake. The effect of each agonist was blocked by its respective antagonist. Furthermore, injection of quinpirole, but not SKF 38393, decreased the mRNA level of preproorexin. In addition, injection of SKF 38393 decreased the mRNA levels of neuropeptide Y and agouti-related peptide, whereas the injection of quinpirole increased the mRNA level of proopiomelanocortin. These results indicate that food intake activates dopamine neurons projecting from the VTA/SNC to the LH through an increase in blood glucose levels, which terminates food intake by stimulation of dopamine D-1 and D-2 receptors. It is also possible that stimulation of dopamine D-1 and D2 receptors in the LH inhibits feeding behavior through different neuropeptides. (C) 2019 Elsevier Inc. All rights reserved.

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