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Cholinergic innervation of the prefrontal cortex is critical for various forms of cognition, although the efferent modulators contributing to acetylcholine (ACh) release are not well understood. The main source of cortical ACh, the basal forebrain, receives projections from lateral and perifornical hypothalamic neurons releasing the peptides orexin (orexin A; OxA, and orexin B; OxB), of which OxA is hypothesized to play a role in various cognitive functions. We sought to assess one such function known to be susceptible to basal forebrain cholinergic manipulation, olfactory discrimination acquisition, and reversal learning, in rats following intra-basal forebrain infusion of OxA or the orexin 1 receptor (OxR1) antagonist SB-334867. OxA administration facilitated, while OxR1 antagonism impaired performance on both the acquisition and reversal portions of the task. These data suggest that orexin acting in the basal forebrain may be important for cortical-dependant executive functions, possibly through the stimulation of cortical ACh release.

Original publication

DOI

10.1016/j.brainres.2014.10.041

Type

Journal article

Journal

Brain Res

Publication Date

12/01/2015

Volume

1594

Pages

215 - 222

Keywords

Basal forebrain, Cholinergic, Cognitive flexibility, Nucleus basalis, Orexin, SB-334867, Animals, Basal Forebrain, Executive Function, Intracellular Signaling Peptides and Proteins, Learning, Male, Microdialysis, Neuropeptides, Olfactory Perception, Orexin Receptors, Orexins, Rats, Rats, Sprague-Dawley