Back to Search
Start Over
Pharmacologic rescue of impaired cognitive flexibility, social deficits, increased aggression, and seizure susceptibility in oxytocin receptor null mice: a neurobehavioral model of autism
- Source :
- Biological psychiatry. 69(9)
- Publication Year :
- 2010
-
Abstract
- Background Oxytocin (OT) has been suggested as a treatment to improve social behavior in autistic patients. Accordingly, the OT ( Oxt −/− ) and the OT receptor null mice ( Oxtr −/− ) display autistic-like deficits in social behavior, increased aggression, and reduced ultrasonic vocalization. Methods Oxtr −/− mice were characterized for general health, sociability, social novelty, cognitive flexibility, aggression, and seizure susceptibility. Because vasopressin (AVP) and OT cooperate in controlling social behavior, learning, and aggression, they were tested for possible rescue of the impaired behaviors. Primary hyppocampal cultures from Oxtr +/+ and Oxtr −/− mouse embryos were established to investigate the balance between gamma-aminobutyric acid (GABA) and glutamate synapses and the expression levels of OT and AVP (V1a) receptors were determined by autoradiography. Results Oxtr −/− mice display two additional, highly relevant, phenotypic characteristics: 1) a resistance to change in a learned pattern of behavior, comparable to restricted interests and repetitive behavior in autism, and 2) an increased susceptibility to seizures, a frequent and clinically relevant symptom of autism. We also show that intracerebral administration of both OT and AVP lowers aggression and fully reverts social and learning defects by acting on V1a receptors and that seizure susceptibility is antagonized by peripherally administered OT. Finally, we detect a decreased ratio of GABA–ergic versus total presynapses in hippocampal neurons of Oxtr −/− mice. Conclusions Autistic-like symptoms are rescued on administration of AVP and OT to young Oxtr −/− adult animals. The Oxtr −/− mouse is thus instrumental to investigate the neurochemical and synaptic abnormalities underlying autistic-like disturbances and to test new strategies of pharmacologic intervention.
- Subjects :
- Male
medicine.medical_specialty
Vasopressin
Neuropeptide
Oxytocin
Hippocampus
Mice
Neurochemical
Cognition
Seizures
Internal medicine
Convulsion
medicine
Animals
Autistic Disorder
Social Behavior
BIO/14 - FARMACOLOGIA
Biological Psychiatry
Cells, Cultured
Mice, Knockout
Neurons
Analysis of Variance
Aggression
Glutamate receptor
Oxytocin receptor
Immunohistochemistry
Arginine Vasopressin
Disease Models, Animal
Endocrinology
Receptors, Oxytocin
Autoradiography
medicine.symptom
Aggression/*drug effects/physiology, Analysis of Variance, Animals, Arginine Vasopressin/metabolism, /*pharmacology, Autistic Disorder, Autoradiography, Cells, Cultured, Cognition/*drug effects/physiology, Disease Models, Animal Hippocampus/cytology/drug, effects/metabolism, Immunohistochemistry, Male, Mice, Mice, Knockout, Neurons/cytology/drug effects/metabolism, Oxytocin/metabolism/*pharmacology, Receptors, Oxytocin/*genetics, Seizures/genetics/*physiopathology, *Social Behavior
Psychology
Neuroscience
medicine.drug
Subjects
Details
- ISSN :
- 18732402
- Volume :
- 69
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Biological psychiatry
- Accession number :
- edsair.doi.dedup.....7f77ddb5d8204ab9bb393e1c0ee31229