title: Anxious behavior induces elevated hippocampal Cb2receptor gene expression.
abstract: Anxiety is differentially expressed across a continuum of stressful/fearful intensity, influenced by endocannabinoid systems and receptors. The hippocampus plays important roles in the regulation of affective behavior, emotion, and anxiety, as well as memory. Location of Cb1/Cb2receptor action could be important in determining emotional valence, because while the dorsal hippocampus is involved in spatial memory and cognition, the ventral hippocampus has projections to the PFC, BNST, amygdala, and HPA axis, and is important for emotional responses to stress. During repeated social defeat in a Stress-Alternatives Model arena (SAM; an oval open field with escape portals only large enough for smaller mice), smaller C57BL6/N mice are subject to fear conditioning (tone=CS), and attacked by novel larger aggressive CD1 mice (US) over four daily (5min) trials. Each SAM trial presents an opportunity for escape or submission, with stable behavioral responses established by the second day of interaction. Additional groups had access to a running wheel. Social aggression plus fear conditioning stimulates enhanced Cb2receptor gene expression in the dorsal CA1, dorsal and ventral dentate gyrus subregions in animals displaying a submissive behavioral phenotype. Escape behavior is associated with reduced Cb2expression in the dorsal CA1region, with freezing and escape latency correlated with mRNA levels. Escaping and submitting animals with access to running wheels had increased Cb2mRNA in dorsal DG/CA1. These results suggest that the Cb2receptor system is rapidly induced during anxiogenic social interactions plus fear conditioning or exercise; with responses potentially adaptive for coping mechanisms.
authors.affiliation: Department of Biology, University of South Dakota, Vermillion, SD 57069, USA; Neuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Robertson
authors.affiliation: Department of Biology, University of South Dakota, Vermillion, SD 57069, USA; Neuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA; Veterans Affairs Research Service, Sioux Falls VA Health Care System, Sioux Falls, SD 57105, USA; Avera McKennan Hospital & University Health Center, Sioux Falls, SD 57105, USA.
authors.forename: Justin K
authors.initials: JK
authors.lastname: Achua
authors.affiliation: Department of Biology, University of South Dakota, Vermillion, SD 57069, USA; Neuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA; Veterans Affairs Research Service, Sioux Falls VA Health Care System, Sioux Falls, SD 57105, USA; Institute of Possibility, 322 E. 8th Street, Suite 302, Sioux Falls, SD 57103, USA; Sanford Health, 2301 E. 60th St. N., Sioux Falls, SD 57104, USA.
authors.forename: Justin P
authors.initials: JP
authors.lastname: Smith
authors.affiliation: Department of Biology, University of South Dakota, Vermillion, SD 57069, USA; Neuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA; Veterans Affairs Research Service, Sioux Falls VA Health Care System, Sioux Falls, SD 57105, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Prince
authors.affiliation: Department of Biology, University of South Dakota, Vermillion, SD 57069, USA; Neuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA; Veterans Affairs Research Service, Sioux Falls VA Health Care System, Sioux Falls, SD 57105, USA.
authors.forename: Clarissa D
authors.initials: CD
authors.lastname: Staton
authors.affiliation: Neuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA; Veterans Affairs Research Service, Sioux Falls VA Health Care System, Sioux Falls, SD 57105, USA; Department of Psychiatry, University of South Dakota School of Medicine Vermillion, SD, USA; Laboratory for Clinical and Translational Research in Psychiatry, Department of Veterans Affairs Medical Center, Denver, CO 80220, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Ronan
authors.affiliation: Department of Biology, University of South Dakota, Vermillion, SD 57069, USA; Neuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA; Veterans Affairs Research Service, Sioux Falls VA Health Care System, Sioux Falls, SD 57105, USA.
authors.forename: Tangi R
authors.initials: TR
authors.lastname: Summers
authors.affiliation: Department of Biology, University of South Dakota, Vermillion, SD 57069, USA; Neuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA; Veterans Affairs Research Service, Sioux Falls VA Health Care System, Sioux Falls, SD 57105, USA. Electronic address: Cliff@USD.Edu.
authors.forename: Cliff H
authors.initials: CH
authors.lastname: Summers
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects; D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology; D004195:Disease Models, Animal; D004924:Escape Reaction / Q000502:physiology; D005239:Fear / Q000523:psychology; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D007398:Interpersonal Relations; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010805:Physical Conditioning, Animal / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics* / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological / Q000473:pathology* / Q000503:physiopathology
chemical_list: D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D011990:Receptors, Transferrin; C480029:Tfrc protein, mouse
keywords: Cb(2); anxiety; endocannabinoid; exercise; hippocampus; induction