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: Serotonin transporter (SERT) and brain-derived neurotrophic factor (BDNF) are key modulators of molecular signaling, cognition and behavior. Although SERT and BDNF mutant mouse phenotypes have been extensively characterized, little is known about their self-grooming behavior. Grooming represents an important behavioral domain sensitive to environmental stimuli and is increasingly used as a model for repetitive behavioral syndromes, such as autism and attention deficit/hyperactivity disorder. The present study used heterozygous ((+/-)) SERT and BDNF male mutant mice on a C57BL/6J background and assessed their spontaneous self-grooming behavior applying both manual and automated techniques. Overall, SERT(+/-) mice displayed a general increase in grooming behavior, as indicated by more grooming bouts and more transitions between specific grooming stages. SERT(+/-) mice also aborted more grooming bouts, but showed generally unaltered activity levels in the observation chamber. In contrast, BDNF(+/-) mice displayed a global reduction in grooming activity, with fewer bouts and transitions between specific grooming stages, altered grooming syntax, as well as hypolocomotion and increased turning behavior. Finally, grooming data collected by manual and automated methods (HomeCageScan) significantly correlated in our experiments, confirming the utility of automated high-throughput quantification of grooming behaviors in various genetic mouse models with increased or decreased grooming phenotypes. Taken together, these findings indicate that mouse self-grooming behavior is a reliable behavioral biomarker of genetic deficits in SERT and BDNF pathways, and can be reliably measured using automated behavior-recognition technology.Brain research bulletin 08/2012; 89(5-6):168-76. · 2.18 Impact Factor
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ABSTRACT: It is well known that emotions participate in the regulation of social behaviors and that the emotion displayed by a conspecific influences the behavior of other animals. In its simplest form, empathy can be characterized as the capacity to be affected by and/or share the emotional state of another. However, to date, relatively little is known about the mechanisms by which animals that are not in direct danger share emotions. In the present study, we used a model of between-subject transfer of fear to characterize the social interaction during which fear is transmitted, as well as the behavioral effects of socially transmitted fear. We found that (1) during social interaction with a recently fear-conditioned partner, observers and demonstrators exhibit social exploratory behaviors rather than aggressive behaviors; (2) learning and memory in a shock-motivated shuttle avoidance task are facilitated in rats that underwent a social interaction with a partner that had been fear conditioned; and (3) a brief social interaction with a recently fear-conditioned partner immediately before fear conditioning increases conditioned freezing measured on the next day. The observed effects were not due to a stress-induced increase in pain sensitivity or analgesia. Collectively, these data suggest that a brief social interaction with a cage mate that has undergone an aversive learning experience promotes aversive learning in an otherwise naïve animal. We argue that socially transferred fear is an adaptation that promotes defensive behavior to potentially dangerous situations in the environment.Learning & memory (Cold Spring Harbor, N.Y.) 01/2010; 17(1):35-42. · 4.08 Impact Factor
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ABSTRACT: In the present manuscript we review a substantial body of literature describing several pre-clinical animal models designed and developed with the purpose of investigating the biological determinants of Tourette Syndrome (TS). In order to map the animal models onto the theoretical background upon which they have been devised, we first define phenomenological and etiological aspects of TS and then match this information to the available pre-clinical models. Thus, we first describe the characteristic symptoms exhibited by TS patients and then a series of hypotheses attempting to identify the multifactorial causes of TS. With respect to the former, we detail the phenomenology of abnormal repetitive behaviors (tics and stereotypies), obsessive-compulsive behaviors and aberrant sensory-motor gating. With respect to the latter, we describe both potential candidate vulnerability genes and environmental factors (difficult pregnancies, psychosocial stressors and infections). We then discuss how this evidence has been translated in pre-clinical research with respect to both dependent (symptoms) and independent (etiological factors) variables. Thus, while, on the one hand, we detail the methodologies adopted to measure abnormal repetitive and obsessive-compulsive behaviors, and sensory-motor gating, on the other hand, we describe genetic engineering studies and environmental modulations aimed at reproducing the proposed biological determinants in laboratory rodents. A special emphasis is placed upon "programming" events, occurring during critical stages of early development and exerting organizational delayed consequences. In the final section, we outline a heuristic model with the purpose of integrating clinical and pre-clinical evidence in the study of TS.Neuroscience & Biobehavioral Reviews 04/2013; · 10.28 Impact Factor