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Orexin lesions block food-related increases in cortical acetylcholine release

Fadel J, Frederick-Duus D, Butts R (2005) Orexin lesions block food-related increases in cortical acetylcholine release. Neuroscience 2005 Abstracts 644.8. Society for Neuroscience, Washington, DC.

Summary: Hypothalamic orexin (hypocretin) neurons influence and coordinate arousal, state-dependent behavior, feeding and metabolic processes. Orexin fibers are seen in close proximity to choline acetyltransferase (ChAT)-positive magnocellular somata in portions of the basal forebrain and intrabasalis administration of orexin A increases cortical acetylcholine (ACh) release, suggesting that orexin inputs to the basal forebrain may be important for biasing attentional resources toward stimuli related to underlying homeostatic challenges. Here, we mildly food-deprived rats and trained them to associate an environmental stimulus (darkness) with presentation of palatable food. Microdialysis in these animals showed that the darkness stimulus, with or without accompanying food presentation, produced a robust increase in cortical ACh release. A subset of animals received unilateral administration of the immunotoxin orexin B-saporin (OxB-SAP; 350 ng/0.5 μl) or vehicle into the lateral hypothalamus and perifornical area. OxB-SAP produced a substantial (70-80%) ipsilateral loss of orexin-immunoreactive cells and a corresponding decrease in orexin fiber density in the basal forebrain. OxB-SAP did not alter the number or basal forebrain neurons showing ChAT-immunoreactivity and produced only mild (approximately 15%) loss of melanin-concentrating hormone cells. Basal cortical ACh release was unaffected in lesioned animals, but OxB-SAP lesions abolished increases in cortical ACh release associated with the food-paired stimulus. These data indicate that orexin inputs to the basal forebrain are required for food anticipatory-related increases in cortical ACh release. Orexins appear to be important components of the neural pathways by which interoceptive cues related to homeostasis recruit forebrain attentional systems.

Related Products: Orexin-B-SAP (Cat. #IT-20)

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