Social withdrawal, neophobia, and stereotyped behavior in developing rats exposed to neonatal asphyxia.
ABSTRACT Perinatal asphyxia is a concern for public health and may promote subtle neuropsychiatric disorders. Anoxic insults to neonatal rats cause long-lasting neurobehavioral deficits. In the present study, we focussed on changes in emotional behaviors as a consequence of neonatal asphyxia in Wistar rats. Newborn pups (24 h after birth) underwent a single 30-min exposure to a 100% N2 atmosphere (or air). The offspring was tested for a) locomotor and exploratory activity with or without a d-amphetamine challenge (0, 1, or 2 mg/kg) on postnatal day (pnd) 15; b) social interactions and novelty seeking during adolescence; c) levels of the brain-derived neurotrophic factor (BDNF). In the open-field test (pnd 15), N2-exposed pups injected with the high (2 mg/kg) amphetamine dose exhibited reduced levels of locomotor hyperactivity, and a more marked involvement in stereotyped behaviors. Individual differences emerged in the locomotor response to the novelty-seeking test: two subgroups of rats (separated on the basis of the median value) showed either arousal/attraction or avoidance/inhibition in response to free-choice novelty. The N2-exposed group showed a more marked novelty-induced avoidance and inhibition. Time devoted to allogrooming and play-soliciting behaviors was reduced, whereas object exploration was increased. Levels of BDNF were reduced in the striatum of N2-exposed rats, suggesting poorer synaptic performance of dopamine pathways. In conclusion, these findings suggest an increased risk of developing social withdrawal, neophobia and behavioral stereotypies (common symptoms found in schizophrenia and autism) as a consequence of neonatal asphyxia in preterm humans.
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ABSTRACT: The preclinical study of human disorders associated with comorbidities and for which the aetiology is still unclear may substantially benefit from multi-strain studies conducted in mice. The latter can help isolating experimental populations (strains) exhibiting distinct facets in the parameters isomorphic to the symptoms of a given disorder. Through a reverse-translation approach, multi-strain studies can inform both natural predisposing factors and environmental modulators. Thus, mouse strains selected for a particular trait may be leveraged to generate hypothesis-driven studies aimed at clarifying the potential role played by the environment in modulating the exhibition of the symptoms of interest. Tourette's syndrome (TS) constitutes a paradigmatic example whereby: it is characterized by a core symptom (tics) often associated with comorbidities (attention-deficit-hyperactivity and obsessive-compulsive symptoms); it has a clear genetic origin though specific genes are, as yet, unidentified; its course (exacerbations and remissions) is under the influence of environmental factors. Based on these considerations, we tested four mouse strains (ABH, C57, CD1, and SJL)-varying along a plethora of behavioural, neurochemical, and immunological parameters-on a test battery tailored to address the following domains: tics (through the i.p. administration of the selective 5-HT2 receptor agonist DOI, 5mg/kg); locomotion (spontaneous locomotion in the home-cage); perseverative responding in an attentional set shifting task; and behavioural stereotypies in response to a single amphetamine (10mg/kg, i.p.) injection. Present data demonstrate that while ABH and SJL mice respectively exhibit selective increments in amphetamine-induced sniffing behaviour and DOI-induced tic-like behaviours, C57 and CD1 mice show a distinct phenotype, compared to other strains, in several parameters.Behavioural brain research 03/2014; · 3.22 Impact Factor
- European Neuropsychopharmacology - EUR NEUROPSYCHOPHARMACOL. 01/2011; 21.
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ABSTRACT: So far, little is known about the comorbidity of substance use disorders ( sud ) and autism spectrum disorders ( asd ). To increase our knowledge of sud in asd patients by means of a broad explorative study. In a cross-sectional study 70 patients with asd were compared with 53 patients with adhd . Both groups included some patients with sud and without sud . Comparisons were drawn at three different levels: phenotype, endophenotype and genotype. At the phenotypical level, risk factors for sud were similar for asd and adhd (early onset smoking, adverse family history, parental addiction). The subgroup asd -with- sud reported better social orientation than the subgroup asd -without - sud , in spite of having impaired functioning at the phenotypical level and more cognitive problems at the endophenotypical level. At the genetic level, asd could be differentiated from adhd on the basis of three candidate genes, but this differentiation was irrespective of sud status. sud occur less frequently with asd than with adhd , but when they occur, they are just as severe. These results have implications for treatment.Tijdschrift voor psychiatrie 01/2013; 55(11):873-8.