title: Dopamine D1 receptor activity is involved in the increased anxiety levels observed in STZ-induced diabetes in rats.
abstract: Epidemiological surveys have indicated that anxiety disorders are more frequent in diabetic patients than in the general population. Similar results have been shown in animal studies using the streptozotocin (STZ)-induced diabetes model. The mechanisms underlying this relationship are not clearly understood, but it has been suggested that alterations in the dopaminergic neurotransmission, which plays an important role in the amygdaloid modulation of fear and anxiety, may be involved. The aim of this study was to ascertain whether or not the amygdaloid DA D1 receptors are involved in the increase of anxiety-like behavior observed in "diabetic" animals. Adult Wistar male rats were injected with STZ (50mg/kg, i.p.) in two consecutive days and subjected to the Shock-Probe Burying Test 10days after the beginning of treatment. STZ-treated rats showed a significant increase in immobility/freezing behavior whereas no effects were elicited in latency to bury, burying behavior itself and the number of shocks received during testing as compared with non-diabetic controls. These results suggest the triggering of a passive coping response in the STZ-treated rats. Interestingly, immobility/freezing behavior was reversed following the intra-amygdaloid dopamine D1 receptor blockade by the local microinfusion of SCH23390 (100ng/side). Autoradiographic experiments showed a selective increase of [(3)H]-SCH23390 binding in the ventral intercalated paracapsular islands of STZ-treated rats when compared to the non-treated control group. Our results suggest that a hyperdopaminergic state involving DA D1 receptors within the amygdala may have a role in the increase of anxiety observed in diabetic rats.
authors.affiliation: Division of Neuroscience, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rebolledo-Solleiro
authors.affiliation: Division of Neuroscience, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: Luis Fernando Ontiveros
authors.initials: LFO
authors.lastname: Araiza
authors.affiliation: Neuroanatomy Research Group, Institute for Psychopharmacology at Central Institute for Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Broccoli
authors.affiliation: Neuroanatomy Research Group, Institute for Psychopharmacology at Central Institute for Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany.
authors.forename: Anita C
authors.initials: AC
authors.lastname: Hansson
authors.affiliation: Department of Pharmacobiology, Instituto de Investigación y Estudios Avanzados (CINVESTAV) Sede Sur, Mexico City, Mexico.
authors.forename: Luisa Lilia
authors.initials: LL
authors.lastname: Rocha-Arrieta
authors.affiliation: Division of Neuroscience, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: Raúl
authors.initials: R
authors.lastname: Aguilar-Roblero
authors.affiliation: Division of Neuroscience, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: Minerva
authors.initials: M
authors.lastname: Crespo-Ramírez
authors.affiliation: Division of Cellular and Molecular Neurochemistry, Department of Neuroscience, Karolinska Institutet, Sweden.
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
authors.affiliation: Division of Neuroscience, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico. Electronic address: mperez@ifc.unam.mx.
authors.forename: Miguel
authors.initials: M
authors.lastname: Pérez de la Mora
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000378:metabolism*; D001008:Anxiety Disorders / Q000188:drug therapy / Q000378:metabolism; D001552:Benzazepines / Q000494:pharmacology; D005239:Fear / Q000187:drug effects / Q000502:physiology; D008297:Male; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D013311:Streptozocin; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D001552:Benzazepines; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D013311:Streptozocin
keywords: Amygdala; Anxiety; Diabetes; Dopamine; Intercalated islands; Shock/Probe Burying Test