title: Behavioural and transcriptional effects of escitalopram in the chronic escape deficit model of depression.
abstract: The study of depression is facing major challenges: first, the need to develop new drugs with a faster onset of action and second, fulfilling the unmet needs of treatment resistant patients with more effective compounds. The chronic escape deficit (CED) is a valid and useful model of depression and is based on the induction of an escape deficit after exposure of rats to an unavoidable stress. This behavioural model provides a method for evaluating the capacity of a treatment to revert the escape deficit. The majority of antidepressant drugs need to be administered for at least 3-4 weeks in order to revert the escape deficit. A 7-day treatment with escitalopram reverted the stress-induced escape deficit in approximately 50% of the animals. Escitalopram treatment decreased anxiety-related behaviours in stressed animals, by increasing the time spent in the central part of the arena with respect to saline treated stressed animals, without affecting exploratory related behaviours. Gene expression profiling was carried out in the hippocampus to identify new targets associated with the effects of stress or with the different response to escitalopram. By combining a well-validated animal model with gene expression analysis we demonstrated that the CED model may represent a perfect tool for studying treatment-resistant depression.
authors: Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41125 Modena, Italy.
authors: Cristina
authors: C
authors: Benatti
authors: Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41125 Modena, Italy.
authors: Silvia
authors: S
authors: Alboni
authors: Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Via del Pozzo 71, 41125 Modena, Italy.
authors: Joan M C
authors: JM
authors: Blom
authors: Genethon, 1 bis, rue de l'Internationale, 91000 Evry, France.
authors: Francesco
authors: F
authors: Gandolfi
authors: Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Free University of Brussels, 808 Route de Lennik, Brussels, Belgium.
authors: Julien
authors: J
authors: Mendlewicz
authors: Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41125 Modena, Italy.
authors: Nicoletta
authors: N
authors: Brunello
authors: Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41125 Modena, Italy. Electronic address: fabio.tascedda@unimore.it.
authors: Fabio
authors: F
authors: Tascedda
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology; D001835:Body Weight; D002908:Chronic Disease; D015283:Citalopram / Q000494:pharmacology*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004924:Escape Reaction; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D046228:Microarray Analysis; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009483:Neuropsychological Tests; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000188:drug therapy / Q000503:physiopathology; D013997:Time Factors
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram
keywords: Animal model of depression; Anxiety; Escitalopram; Hippocampus; Treatment-resistant depression