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Regulation of the Mouse Ventral Tegmental Area by Melanin-Concentrating Hormone.
Spencer, Carl Duncan; Miller, Persephone A; Williams-Ikhenoba, Jesukhogie G; Nikolova, Ralitsa G; Chee, Melissa J.
Afiliação
  • Spencer CD; Department of Neuroscience, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
  • Miller PA; Department of Neuroscience, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
  • Williams-Ikhenoba JG; Department of Neuroscience, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
  • Nikolova RG; Department of Neuroscience, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
  • Chee MJ; Department of Neuroscience, Carleton University, Ottawa, Ontario K1S 5B6, Canada melissa.chee@carleton.ca.
J Neurosci ; 44(27)2024 Jul 03.
Article em En | MEDLINE | ID: mdl-38806249
ABSTRACT
Melanin-concentrating hormone (MCH) acts via its sole receptor MCHR1 in rodents and is an important regulator of homeostatic behaviors like feeding, sleep, and mood to impact overall energy balance. The loss of MCH signaling by MCH or MCHR1 deletion produces hyperactive mice with increased energy expenditure, and these effects are consistently associated with a hyperdopaminergic state. We recently showed that MCH suppresses dopamine release in the nucleus accumbens, which principally receives dopaminergic projections from the ventral tegmental area (VTA), but the mechanisms underlying MCH-regulated dopamine release are not clearly defined. MCHR1 expression is widespread and includes dopaminergic VTA cells. However, as the VTA is a neurochemically diverse structure, we assessed Mchr1 gene expression at glutamatergic, GABAergic, and dopaminergic VTA cells and determined if MCH inhibited the activity of VTA cells and/or their local microcircuit. Mchr1 expression was robust in major VTA cell types, including most dopaminergic (78%) or glutamatergic cells (52%) and some GABAergic cells (38%). Interestingly, MCH directly inhibited dopaminergic and GABAergic cells but did not regulate the activity of glutamatergic cells. Rather, MCH produced a delayed increase in excitatory input to dopamine cells and a corresponding decrease in GABAergic input to glutamatergic VTA cells. Our findings suggested that MCH may acutely suppress dopamine release while disinhibiting local glutamatergic signaling to restore dopamine levels. This indicated that the VTA is a target of MCH action, which may provide bidirectional regulation of energy balance.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hormônios Hipofisários / Área Tegmentar Ventral / Neurônios Dopaminérgicos / Hormônios Hipotalâmicos / Melaninas Limite: Animals Idioma: En Revista: J Neurosci Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hormônios Hipofisários / Área Tegmentar Ventral / Neurônios Dopaminérgicos / Hormônios Hipotalâmicos / Melaninas Limite: Animals Idioma: En Revista: J Neurosci Ano de publicação: 2024 Tipo de documento: Article