title: Widespread blunting of hypothalamic and amygdala-septal activity and behavior in rats with long-term hyperglycemia.
abstract: Anxiety and depression in diabetic patients contributes to a poor prognosis, but possible causal relationships have been controversial. Anxiety, fear, and anhedonia are mediated by interactions between different deep structures of the temporal lobe (e.g., amygdala complex and hippocampus) and other forebrain-related structures (e.g., lateral septal nucleus). Connections between these structures and the hypothalamic orexinergic system are necessary for the maintenance of energy and wakefulness. However, few studies have explored the impact of long-term hyperglycemia in these structures on anxiety. We induced long-term hyperglycemia (glucose levels of ∼500mg/dl) in Wistar rats by injecting them with alloxan and simultaneously protecting them from hyperglycemia by injecting them daily with a low dose of insulin (i.e., just enough insulin to avoid death), thus maintaining hyperglycemia and ketonuria for as long as 6 weeks. Compared with controls, long-term hyperglycemic rats exhibited a significant reduction of Fos expression in the lateral septal nucleus and basolateral amygdala, but no differences were found in cerebellar regions. Orexin-A cells appeared to be inactive in the lateral hypothalamus. No differences were found in sucrose consumption or behavior in the elevated plus maze compared with the control group, but a decrease in general locomotion was observed. These data indicate a generalized blunting of the metabolic brain response, accompanied by a decrease in locomotion but no changes in hedonic- or anxiety-like behavior.
authors.affiliation: Área de Biología y Salud Integral, Instituto de Investigaciones Biológicas, Universidad Veracruzana, Xalapa, Veracruz, Mexico.
authors.forename: M L
authors.initials: ML
authors.lastname: Moreno-Cortés
authors.affiliation: Laboratorio de Neurofarmacología, Instituto de Neuroetología, Universidad Veracruzana, Xalapa, Veracruz, Mexico; Facultad de Psicología, Universidad Veracruzana, Xalapa, Veracruz, Mexico.
authors.forename: A G
authors.initials: AG
authors.lastname: Gutiérrez-García
authors.affiliation: Laboratorio de Neurofarmacología, Instituto de Neuroetología, Universidad Veracruzana, Xalapa, Veracruz, Mexico.
authors.forename: G
authors.initials: G
authors.lastname: Guillén-Ruiz
authors.affiliation: Área de Biología y Salud Integral, Instituto de Investigaciones Biológicas, Universidad Veracruzana, Xalapa, Veracruz, Mexico.
authors.forename: T
authors.initials: T
authors.lastname: Romo-González
authors.affiliation: Laboratorio de Neurofarmacología, Instituto de Neuroetología, Universidad Veracruzana, Xalapa, Veracruz, Mexico; Unidad Periférica-Xalapa, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México. México D.F., Mexico. Electronic address: ccontreras@uv.mx.
authors.forename: C M
authors.initials: CM
authors.lastname: Contreras
mesh_terms: D000496:Alloxan; D000679:Amygdala / Q000378:metabolism* / Q000473:pathology; D059445:Anhedonia; D000818:Animals; D001007:Anxiety; D002908:Chronic Disease; D019422:Dietary Sucrose; D004195:Disease Models, Animal; D006943:Hyperglycemia / Q000378:metabolism* / Q000473:pathology / Q000523:psychology; D007031:Hypothalamus / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007662:Ketosis / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D008297:Male; D009043:Motor Activity / Q000502:physiology; D000068797:Orexins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017208:Rats, Wistar; D020665:Septum of Brain / Q000378:metabolism* / Q000473:pathology
chemical_list: D019422:Dietary Sucrose; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos; D000496:Alloxan
keywords: Amygdala-septal area; Anhedonia; Anxiety; Diabetes; Fos; Orexinergic system