Back to Search
Start Over
Dopamine depresses melanin concentrating hormone neuronal activity through multiple effects on α2-noradrenergic, D1 and D2-like dopaminergic receptors
- Source :
- Neuroscience, Neuroscience, Elsevier-International Brain Research Organization, 2011, 178, pp.89-100. ⟨10.1016/j.neuroscience.2011.01.030⟩
- Publication Year :
- 2010
-
Abstract
- International audience; Two neuronal populations of the lateral hypothalamus that, respectively, produce melanin-concentrating hormone (MCH) and orexin peptides are crucially involved in control of metabolism, feeding and related goal-oriented behaviors. In contrast to orexin neurons, mainly involved in short-term regulation of feeding, MCH neurons participate in long-term control of energy storage and body weight. Beyond its effect on feeding, MCH has also been shown to be involved in regulation of seeking behavior and addiction through modulation of dopamine (DA) metabolism. This regulation is essential for reinforcement-associated behaviors. Moreover, drugs of abuse, which increase extracellular DA levels, are known to decrease food intake. Consistent with this observation, DA has been shown to modulate orexin neurons of the lateral hypothalamus. However, no study is available concerning the effects of DA on MCH neurons. Whole-cell patch-clamp recordings were done in hypothalamic mouse brain slices. MCH neurons were identified by Tau-Cyan-GFP labeling using a transgenic mouse model (MCH-GFP). First, we show that DA (10-200 μM) induces an outward current in MCH neurons. However, this current is not due to activation of DA receptors, but mediated through activation of α2-noradrenergic receptors and subsequent opening of G-protein activated inward rectifier K+ (GIRK) channels. Current-clamp experiments revealed that this GIRK-activation leads to hyperpolarization, thus decreasing excitability of MCH neurons. Furthermore, we confirm that MCH neurons receive mainly GABAergic inputs rather than glutamatergic ones. We show that DA modulates these inputs in a complex manner: at low concentrations, DA activates D1-like receptors, promoting presynaptic activity, whereas, at higher concentrations (100 μM), D2-like receptor activation inhibits presynaptic activity. Overall, DA should lead to a decrease in MCH neuron excitability, likely resulting in down-regulation of MCH release and feeding behavior.
- Subjects :
- Male
Patch-Clamp Techniques
Lateral hypothalamus
Dopamine
MESH: Neurons
Action Potentials
MESH: Receptors, Dopamine D1
Synaptic Transmission
MESH: Dose-Response Relationship, Drug
Membrane Potentials
chemistry.chemical_compound
Mice
0302 clinical medicine
MESH: Receptors, Dopamine D2
MESH: Melanins
Premovement neuronal activity
MESH: Animals
Neurotransmitter
MESH: Action Potentials
Neurons
0303 health sciences
Hypothalamic Hormones
General Neuroscience
respiratory system
medicine.anatomical_structure
MESH: Pituitary Hormones
Dopamine receptor
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
hormones, hormone substitutes, and hormone antagonists
medicine.drug
medicine.medical_specialty
MESH: Mice, Transgenic
Hypothalamus
Mice, Transgenic
MESH: Dopamine
Biology
03 medical and health sciences
MESH: Mice, Inbred C57BL
Receptors, Adrenergic, alpha-2
Internal medicine
MESH: Patch-Clamp Techniques
medicine
MESH: Synaptic Transmission
MESH: Membrane Potentials
Animals
G protein-coupled inwardly-rectifying potassium channel
MESH: Mice
030304 developmental biology
Melanins
Dose-Response Relationship, Drug
Receptors, Dopamine D2
Receptors, Dopamine D1
MESH: Hypothalamus
MESH: Male
Orexin
MESH: Hypothalamic Hormones
Mice, Inbred C57BL
Pituitary Hormones
Endocrinology
chemistry
nervous system
MESH: Receptors, Adrenergic, alpha-2
Neuron
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 18737544 and 03064522
- Volume :
- 178
- Database :
- OpenAIRE
- Journal :
- Neuroscience
- Accession number :
- edsair.doi.dedup.....b5381332c67a43f2a1abdf9662b8c9c8