The Brattleboro Rat Displays a Natural Deficit in Social Discrimination That Is Restored by Clozapine and A Neurotensin Analog

Autor: Philip Y. T. Liu, David Feifel, Joseph R. Goldenberg, Sharon Mexal, Paul D. Shilling, Gilia Melendez
Rok vydání: 2009
Předmět:
Male
neurotensin
Medical and Health Sciences
cognitive deficit
chemistry.chemical_compound
Brattleboro rat
Receptors
Receptors
Neurotensin
Antipsychotics
Clozapine
Neurotensin
Prepulse inhibition
Psychiatry
biology
Mental Disorders
Rats
Brattleboro
Brain
Social Discrimination
Brattleboro Rat
Psychiatry and Mental health
Schizophrenia
Schizophrenic Psychology
Drug
medicine.symptom
Psychology
Antipsychotic Agents
medicine.drug
medicine.medical_specialty
Psychosis
medicine.drug_class
Atypical antipsychotic
Cognitive Deficit
Article
Dose-Response Relationship
social discrimination
Internal medicine
medicine
Animals
Rats
Long-Evans
Social Behavior
Cognitive deficit
Pharmacology
Dose-Response Relationship
Drug
Animal
animal model
Psychology and Cognitive Sciences
Long-Evans
biology.organism_classification
medicine.disease
Rats
schizophrenia
Disease Models
Animal
Endocrinology
chemistry
Disease Models
Exploratory Behavior
Brattleboro
Animal Model
Cognition Disorders
Neuroscience
Zdroj: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, vol 34, iss 8
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
ISSN: 1740-634X
0893-133X
DOI: 10.1038/npp.2009.15
Popis: Cognitive deficits in schizophrenia are a major source of dysfunction for which more effective treatments are needed. The vasopressin-deficient Brattleboro (BRAT) rat has been shown to have several natural schizophrenia-like deficits, including impairments in prepulse inhibition and memory. We investigated BRAT rats and their parental strain, Long Evans (LE) rats, in a social discrimination paradigm, which is an ethologically-relevant animal test of cognitive deficits of schizophrenia based upon the natural preference of animals to investigate conspecifics. We also investigated the effects of the atypical antipsychotic, clozapine and the putative antipsychotic, PD149163, a brain-penetrating neurotensin-1 analogue, on social discrimination in these rats. Adult rats were administered saline or one of three doses of clozapine (0.1, 1.0 or 10 mg/kg) or PD149163 (0.1, 0.3 or 1.0 mg/kg), subcutaneously. Following drug administration, adult rats were exposed to a juvenile rat for a 4-minute learning period. Animals were then housed individually for 30 minutes and then simultaneously exposed to the previously presented juvenile and a new juvenile for 4 minutes. Saline-treated LE rats, but not BRAT rats, exhibited intact social discrimination as evidenced by greater time spent exploring the new juvenile. The highest dose of clozapine and the two highest doses of PD149163 restored social discrimination in BRAT rats. These results provide further support for the utility of the BRAT rat as a genetic animal model relevant to schizophrenia and drug discovery. The potential of neurotensin agonists as putative treatments for cognitive deficits of schizophrenia was also supported.
Databáze: OpenAIRE
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