Stimulation of cortical acetylcholine release by orexin A.
The basal forebrain cholinergic system is a critical component of the neurobiological substrates underlying attentional function. Orexin neurons are important for arousal and maintenance of wakefulness and are found in the area of the hypothalamus previously shown to project to the basal forebrain. We used dual-probe in vivo microdialysis in rats to test the hypothesis that orexin A (OxA) increases cortical acetylcholine (ACh) release. Intrabasalis administration of OxA (0, 0.1, 10.0 microM via reverse dialysis) dose-dependently increased ACh release within the prefrontal cortex (PFC). In a separate group of animals, local (intra-PFC) administration of OxA via reverse dialysis was found to have no significant effect on ACh release. In order to obtain anatomical corroboration of the basal forebrain as a site of orexin modulation of corticopetal cholinergic activity, we used immunohistochemistry to examine the relationship between orexin fibers and cholinergic neurons in the basal forebrain. We observed widespread distribution of orexin-immunoreactive fibers in cholinergic regions of the basal forebrain, particularly in more rostral areas where frequent instances of apparent appositional contact were observed between orexin fibers and choline acetyltransferase-positive cell bodies. Collectively, these data suggest that orexin projections to the basal forebrain form an important link between hypothalamic arousal and forebrain attentional systems.
Fadel
J
J
Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29208, USA. jrfadel@med.sc.edu
Pasumarthi
R
R
Reznikov
L R
LR
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology*; D001288:Attention / Q000187:drug effects / Q000502:physiology; D020532:Basal Nucleus of Meynert / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology; D000068797:Orexins; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine