Melanin concentrating hormone innervation of caudal brainstem areas involved in gastrointestinal functions and energy balance

Neuroscience. 2005;135(2):611-25. doi: 10.1016/j.neuroscience.2005.06.055.


Neural signaling by melanin-concentrating hormone and its receptor (SLC-1) has been implicated in the control of energy balance, but due to the wide distribution of melanin-concentrating hormone-containing fibers throughout the neuraxis, its critical sites of action for a particular effect have not been identified. The present study aimed to anatomically and functionally characterize melanin-concentrating hormone innervation of the rat caudal brainstem, as this brain area plays an important role in the neural control of ingestive behavior and autonomic outflow. Using retrograde tracing we demonstrate that a significant proportion (5-15%) of primarily perifornical and far-lateral hypothalamic melanin-concentrating hormone neurons projects to the dorsal vagal complex. In the caudal brainstem, melanin-concentrating hormone-ir axon profiles are distributed densely in most areas including the nucleus of the solitary tract, dorsal motor nucleus of the vagus, and sympathetic premotor areas in the ventral medulla. Close anatomical appositions can be demonstrated between melanin-concentrating hormone-ir axon profiles and tyrosine hydroxylase, GABA, GLP-1, NOS-expressing, and nucleus of the solitary tract neurons activated by gastric nutrient infusion. In medulla slice preparations, bath application of melanin-concentrating hormone inhibited in a concentration-dependent manner the amplitude of excitatory postsynaptic currents evoked by solitary tract stimulation via a pre-synaptic mechanism. Fourth ventricular administration of melanin-concentrating hormone (10 microg) in freely moving rats decreased core body temperature but did not change locomotor activity and food and water intake. We conclude that the rich hypothalamo-medullary melanin-concentrating hormone projections in the rat are mainly inhibitory to nucleus of the solitary tract neurons, but are not involved in the control of food intake. Projections to ventral medullary sites may play a role in the inhibitory effect of melanin-concentrating hormone on energy expenditure.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autonomic Nervous System / physiology
  • Axons / metabolism
  • Behavior, Animal
  • Body Temperature / drug effects
  • Body Temperature / physiology
  • Brain Stem / cytology*
  • Brain Stem / metabolism
  • Cell Count / methods
  • Cholera Toxin / metabolism
  • Dose-Response Relationship, Drug
  • Eating / drug effects
  • Eating / physiology
  • Electric Stimulation / methods
  • Energy Metabolism*
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Excitatory Postsynaptic Potentials / radiation effects
  • Feeding Behavior / drug effects
  • Feeding Behavior / physiology*
  • Glucagon-Like Peptide 1 / metabolism
  • Hypothalamic Hormones / metabolism*
  • Hypothalamic Hormones / pharmacology
  • Immunohistochemistry / methods
  • In Vitro Techniques
  • Male
  • Melanins / metabolism*
  • Melanins / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neural Inhibition / radiation effects
  • Neural Pathways / metabolism*
  • Neurons / cytology
  • Neurons / metabolism*
  • Neurons / parasitology
  • Nitric Oxide Synthase / metabolism
  • Patch-Clamp Techniques / methods
  • Pituitary Hormones / metabolism*
  • Pituitary Hormones / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Tyrosine 3-Monooxygenase / metabolism
  • gamma-Aminobutyric Acid / metabolism


  • Hypothalamic Hormones
  • Melanins
  • Pituitary Hormones
  • gamma-Aminobutyric Acid
  • melanin-concentrating hormone
  • Glucagon-Like Peptide 1
  • Cholera Toxin
  • Nitric Oxide Synthase
  • Tyrosine 3-Monooxygenase