title: Exposure to an elevated platform increases plasma corticosterone and hippocampal acetylcholine in the rat: reversal by chlordiazepoxide.
abstract: There is evidence that the septohippocampal cholinergic system is activated in response to stressful stimuli. In addition, prior studies indicate that stimulating the hippocampal cholinergic neurotransmission increases open arm exploration in the elevated plus-maze. This raises the possibility that exposing the rat to an elevated platform, which would be similar to confining the animal to the open arms of the plus-maze, would alter hippocampal acetylcholine levels. Results from the present study suggest that an elevated platform can be used as an animal model of stress in that exposure to the platform significantly increased plasma corticosterone levels. Importantly, exposure to a platform significantly increased hippocampal acetylcholine efflux. Interestingly, the increase in plasma corticosterone and hippocampal acetylcholine levels upon exposure to an elevated platform could be prevented by chlordiazepoxide at a dose that had no effect on basal hippocampal acetylcholine or plasma corticosterone levels. However, the elevated platform-induced increase in hippocampal acetylcholine could not be blocked by prior administration of buspirone. These results provide direct evidence for the importance of the hippocampal cholinergic system in stress and provide validation for the elevated platform as a model of stress.
authors.affiliation: Neuroscience Discovery Research, Eli Lilly and Company, Lilly Corporate Center-DC0510, Indianapolis, IN, 46285-0510, USA.
authors.forename: Aldemar
authors.initials: A
authors.lastname: Degroot
authors.forename: Mark
authors.initials: M
authors.lastname: Wade
authors.forename: Craig
authors.initials: C
authors.lastname: Salhoff
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Davis
authors.forename: Eleni T
authors.initials: ET
authors.lastname: Tzavara
authors.forename: George G
authors.initials: GG
authors.lastname: Nomikos
mesh_terms: D000109:Acetylcholine / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002065:Buspirone / Q000494:pharmacology; D002707:Chlordiazepoxide / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004779:Environment Design; D005110:Extracellular Space / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D005544:Forecasting; D006624:Hippocampus / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D011187:Posture / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000097:blood* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D002707:Chlordiazepoxide; D000109:Acetylcholine; D002065:Buspirone; D003345:Corticosterone