title: Activation of GABAergic pathway by hypocretin in the median raphe nucleus (MRN) mediates stress-induced theta rhythm in rats.
abstract: The frequency of electroencephalograms (EEGs) is predominant in theta rhythm during stress (e.g., footshock) in rats. Median raphe nucleus (MRN) desynchronizes hippocampal theta waves via activation of GABAergic neurons in the medial septum-diagonal band of Broca (MS-DBB), a theta rhythm pacemaker. Increased hypocretin mediates stress responses in addition to the maintenance of wakefulness. Hypocretin receptors are abundant in the MRN, suggesting a possible role of hypocretin in modulating stress-induced theta rhythm. Our results indicated that the intensity of theta waves was enhanced by footshock and that a hypocretin receptor antagonist (TCS1102) suppressed the footshock-induced theta waves. Administration of hypocretin-1 (1 and 10 μg) and hypocretin-2 (10 μg) directly into the MRN simulated the effect of footshock and significantly increased theta waves. Co-administration of GABA(A) receptor antagonist, bicuculline, into the MRN blocked the increase of theta waves induced by hypocretins or footshock. These results suggested that stress enhances the release of hypocretins, activates GABAergic neurons in the MRN, blocks the ability of MRN to desynchronize theta waves, and subsequently increases the intensity of theta rhythm.
authors.affiliation: Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yi-Tse
authors.initials: YT
authors.lastname: Hsiao
authors.forename: Shuo-Bin
authors.initials: SB
authors.lastname: Jou
authors.forename: Pei-Lu
authors.initials: PL
authors.lastname: Yi
authors.forename: Fang-Chia
authors.initials: FC
authors.lastname: Chang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004569:Electroencephalography; D004597:Electroshock / Q000009:adverse effects; D018682:GABA Agents / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D064446:Orexin Receptors; D000068797:Orexins; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000627:therapeutic use; D018013:Receptors, Neuropeptide / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013315:Stress, Psychological / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D013826:Theta Rhythm / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018682:GABA Agents; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D005680:gamma-Aminobutyric Acid