Social Behavior In Rats Research Articles

Pro-social 50-kHz ultrasonic communication in rats: post-weaning but not post-adolescent social isolation leads to social impairments-phenotypic rescue by re-socialization.

Rats are highly social animals and social play during adolescence has an important role for social development, hence post-weaning social isolation is widely used to study the adverse effects of juvenile social deprivation and to induce behavioral phenotypes relevant to neuropsychiatric disorders, like schizophrenia. Communication is an important component of the rat's social behavior repertoire, with ultrasonic vocalizations (USV) serving as situation-dependent affective signals. High-frequency 50-kHz USV occur in appetitive situations and induce approach behavior, supporting the notion that they serve as social contact calls; however, post-weaning isolation effects on the behavioral changes displayed by the receiver in response to USV have yet to be studied. We therefore investigated the impact of post-weaning isolation on socio-affective information processing as assessed by means of our established 50-kHz USV radial maze playback paradigm. We showed that post-weaning social isolation specifically affected the behavioral response to playback of pro-social 50-kHz but not alarm 22-kHz USV. While group-housed rats showed the expected preference, i.e., approach, toward 50-kHz USV, the response was even stronger in short-term isolated rats (i.e., 1 day), possibly due to a higher level of social motivation. In contrast, no approach was observed in long-term isolated rats (i.e., 4 weeks). Importantly, deficits in approach were reversed by peer-mediated re-socialization and could not be observed after post-adolescent social isolation, indicating a critical period for social development during adolescence. Together, these results highlight the importance of social experience for affiliative behavior, suggesting a critical involvement of play behavior on socio-affective information processing in rats.

Distribution of glutamate receptors in the posterodorsal medial amygdala of adult male rats.

The rat posterodorsal medial amygdala (MePD) has a remarkable neuronal plasticity and responds to olfactory/pheromonal stimuli to modulate emotional and reproductive behaviors. Glutamate is locally released by incoming sensorial pathways to establish and enforce synaptic inputs. Here, we combined DiI dye and immunolabeling procedure under confocal microscopy to describe the presence and distribution of glutamate receptors on neurons of the MePD of adult male rats. Western blot analysis interrogated binding specificity. Both AMPA (GluA1-4 subunits) and NMDA (GluN1 subunit) receptors were immunolabeled on cell bodies and along proximal and distal dendritic shafts. AMPA receptors were mainly observed on mushroom and stubby/wide spines, whereas NMDA receptors were found on thin spines. Colocalization of AMPA and NMDA receptors occurred in some spines. Filopodium did not show immunolabeled puncta on it. Our results are different from the distribution of glutamate receptors in the amygdaloid lateral nucleus, an upstream area involved with emotional processing, and suggest a region-specific excitatory transmission at proximal and distal dendritic branches. Altogether, these data provide new information for synaptic processing in the MePD likely related to the modulation of social behavior in rats.

Maternal Style Selectively Shapes Amygdalar Development and Social Behavior in Rats Genetically Prone to High Anxiety

The early-life environment critically influences neurodevelopment and later psychological health. To elucidate neural and environmental elements that shape emotional behavior, we developed a rat model of individual differences in temperament and environmental reactivity. We selectively bred rats for high versus low behavioral response to novelty and found that high-reactive (bred high-responder, bHR) rats displayed greater risk-taking, impulsivity and aggression relative to low-reactive (bred low-responder, bLR) rats, which showed high levels of anxiety/depression-like behavior and certain stress vulnerability. The bHR/bLR traits are heritable, but prior work revealed bHR/bLR maternal style differences, with bLR dams showing more maternal attention than bHRs. The present study implemented a cross-fostering paradigm to examine the contribution of maternal behavior to the brain development and emotional behavior of bLR offspring. bLR offspring were reared by biological bLR mothers or fostered to a bLR or bHR mother and then evaluated to determine the effects on the following: (1) developmental gene expression in the hippocampus and amygdala and (2) adult anxiety/depression-like behavior. Genome-wide expression profiling showed that cross-fostering bLR rats to bHR mothers shifted developmental gene expression in the amygdala (but not hippocampus), reduced adult anxiety and enhanced social interaction. Our findings illustrate how an early-life manipulation such as cross-fostering changes the brain's developmental trajectory and ultimately impacts adult behavior. Moreover, while earlier studies highlighted hippocampal differences contributing to the bHR/bLR phenotypes, our results point to a role of the amygdala as well. Future work will pursue genetic and cellular mechanisms within the amygdala that contribute to bHR/bLR behavior either at baseline or following environmental manipulations.

Increased sociability and gene expression of oxytocin and its receptor in the brains of rats affected prenatally by valproic acid

Autism is a neurodevelopmental disorder characterised by the disruption of social interactions. Autistic animal models play a crucial role in neurophysiologic research on this disorder. One of these models is based on rats that have been prenatally treated with valproic acid — VPA rats. The aim of our study performed with this model was to investigate changes in sociability and gene expression of neuropeptides and receptors involved in regulating social behaviour. We focused on gene expression in the hypothalamus, where the neuropeptides oxytocin (OT) and arginine-vasopressin (AVP) are produced, as well as oxytocin receptors (OTR) in certain neuronal structures involved in the creation of social abilities. Our research showed that VPA rats spent more time in the part with an unknown animal and less time in the central part of a three chamber sociability test apparatus than control animals. The latency period of VPA rats before initiating social contact was decreased. In addition, during weaning, VPA female rats spent more time in direct interaction with an unknown rat. We also found that adult VPA rats had an increased expression of OT in the hypothalamic supraoptic and paraventricular nuclei and of OTR in the medial prefrontal cortex, piriform cortex, cortex–amygdala transition zone and the region of the basolateral and basomedial amygdaloid nuclei compared with controls.To sum up, we observed that a single prenatal injection of VPA increased social behaviour and gene expression of OT and OTR in neurological structures connected with the social behaviour of rats. One unanticipated finding was the absence of one of the core symptoms of autism in VPA rats, suggesting a decreased ability to understand intraspecific communication signals.

Maternal Style Selectively Shapes Amygdalar Development and Social Behavior in Rats Genetically Prone to High Anxiety

Maternal Style Selectively Shapes Amygdalar Development and Social Behavior in Rats Genetically Prone to High Anxiety

Communal nesting exerts epigenetic influences on affective and social behaviors in rats selectively bred for an infantile trait

Communal nesting (CN) is a mouse model of early social enrichment during pregnancy and lactation. In this study, a rat model of CN was developed to determine if CN exerts an epigenetic effect in rats selectively bred for an infantile affective trait (high and low rates of ultrasonic distress calls). High and Low offspring from CN groups were compared to standard reared (SN) offspring on five measures of social and affective behavior at three critical ages. A differential effect of the CN paradigm on High and Low lines was seen in measures of anxiety and arousal, but not in measures of depression or social behavior. Neonatal CN subjects emitted fewer distress calls than SN subjects when separated from their dams, and the High line subjects were more affected by the CN procedure. As juveniles, CN subjects showed increased social behaviors in tests of juvenile parenting and play compared to SN subjects. In adulthood, CN differentially increased the activity of Low line subjects. All CN subjects displayed less anxiety behavior in an open field compared to SN subjects; High line subjects were more anxious than Lows. CN reduced immobility and increased attempts to escape on the Porsolt forced swim task relative to SN subjects. These results extend the usefulness of this early enrichment paradigm from mice to rats, and found some rodent species differences in outcomes dependent on the behavioral test. They also emphasize the importance of social contact during pregnancy and lactation on offspring's optimal development across behaviors and ages.

Strain- and context-dependent effects of the anandamide hydrolysis inhibitor URB597 on social behavior in rats

Genetic and environmental factors play an important role in the cannabinoid modulation of motivation and emotion. Therefore, the aim of the present study was to test whether anandamide modulation of social behavior is strain- and context-dependent. We tested the effects of the anandamide hydrolysis inhibitor URB597 on social behavior and 50-kHz ultrasonic vocalizations (USVs) in adolescent and adult Wistar and Sprague–Dawley rats tested in different emotionally arousing conditions (familiarity/unfamiliarity to the test cage, low/high light).Under all experimental conditions, adolescent and adult Sprague–Dawley rats displayed higher levels of social behavior and emitted more 50-kHz USVs than Wistar rats. URB597 enhanced social play behavior in adolescent Wistar rats under all experimental conditions. However, URB597 only increased social interaction in adult Wistar rats under unfamiliar/high light conditions. URB597 did not affect adolescent social play behavior and adult social interaction in Sprague–Dawley rats under any experimental condition. Moreover, URB597 increased the USVs emitted during social interaction by adolescent Wistar and adult Sprague–Dawley rats tested under familiar/high light and unfamiliar/high light, respectively. These results show that anandamide has distinct roles in adolescent and adult social behaviors. Anandamide modulation of adolescent social play behavior is strain- but not context-dependent. Conversely, anandamide modulation of adult social behavior and USV emission depends upon both strain and experimental context. Furthermore, these results confirm that profound behavioral differences exist between Wistar and Sprague–Dawley rats, which may explain the sometimes contradictory effects of cannabinoid drugs on emotionality in different strains of rodents.

Natural variation in maternal care shapes adult social behavior in rats

Features of the early postnatal environment profoundly shape later physical and behavioral phenotypes. The amount of licking/grooming that rat dams direct towards their offspring has durable consequences, including behavioral and physiological dimensions of stress reactivity, cognition, and reproductive behavior. We examined how natural variation in maternal care alters social behavior in adult offspring and how this relates to anxiety behavior and oxytocin receptor density. Male and female offspring of mothers who received high levels of licking spent significantly more time in social contact with unfamiliar individuals than did offspring whose dams provided less grooming. Reduced anxiety behavior was associated with greater social interaction. No differences in oxytocin receptor binding assessed by (125) I-OVTA autoradiography were detected between groups. The present investigation characterizes a novel impact of maternal care on adult social interaction behavior, replicates anxiety behavior differences, and illustrates connections between social behavior and anxiety in adulthood across maternal treatment groups.

P.1.g.001 Effects of carvedilol on the social behavior of rats submitted to an animal model of mania

P.1.g.001 Effects of carvedilol on the social behavior of rats submitted to an animal model of mania

Phencyclidine affects firing activity of ventral tegmental area neurons that are related to reward and social behaviors in rats

Patients with schizophrenia exhibit deficits in motivation and affect, which suggests an impairment in the reward system. The psychotomimetic drug, phencyclidine (PCP), also induces schizophrenia-like negative symptoms, such as reduced motivation, blunted affect, and social withdrawal in both humans and animals. Previous studies have indicated that the dopaminergic neurons in the ventral tegmental area (VTA) play a pivotal role in the development of reward-associated learning and motivation. However, how PCP affects the activity of VTA neurons during performance of a reward-related task and social interaction with others in unanesthetized animals remains unclear. Here, we recorded the unit activity of VTA neurons in freely moving rats before and after systemic administration of PCP in a classical conditioning paradigm, and during social interaction with an unfamiliar partner. In the classical conditioning task, two different tones were sequentially presented, one of which accompanied electrical stimulation of the medial forebrain bundle as an unconditioned stimulus. After identifying the response properties of recorded neurons in the classical conditioning task and social interaction, animals received an intraperitoneal injection of PCP.Our study demonstrated that most VTA neurons responsive to reward-associated stimuli were also activated during social interaction. Such activation of neurons was considerably suppressed by systemic administration of PCP, thus, PCP may affect the firing activity of VTA neurons that are involved in motivation, learning, and social interaction. Disruption of the response of VTA neurons to reward stimuli and socially interactive situations may be involved in PCP-induced impairments similar to the negative symptoms of schizophrenia.

Altered anxiety-related and abnormal social behaviors in rats exposed to early life seizures

Neonatal seizures are the most common manifestation of neurological dysfunction in the neonate. The prognosis of neonatal seizures is highly variable, and the controversy remains whether the severity, duration, or frequency of seizures may contribute to brain damage independently of its etiology. Animal data indicates that seizures during development are associated with a high probability of long-term adverse effects such as learning and memory impairment, behavioral changes and even epilepsy, which is strongly age dependent, as well as the severity, duration, and frequency of seizures. In preliminary studies, we demonstrated that adolescent male rats exposed to one-single neonatal status epilepticus (SE) episode showed social behavior impairment, and we proposed the model as relevant for studies of developmental disorders. Based on these facts, the goal of this study was to verify the existence of a persistent deficit and if the anxiety-related behavior could be associated with that impairment. To do so, male Wistar rats at 9 days postnatal were submitted to a single episode of SE by pilocarpine injection (380 mg/kg, i.p.) and control animals received saline (0.9%, 0.1 mL/10 g). It was possible to demonstrate that in adulthood, animals exposed to neonatal SE displayed low preference for social novelty, anxiety-related behavior, and increased stereotyped behavior in anxiogenic environment with no locomotor activity changes. On the balance, these data suggests that neonatal SE in rodents leads to altered anxiety-related and abnormal social behaviors.

Sweet Success, Bitter Defeat: A Taste Phenotype Predicts Social Status in Selectively Bred Rats

For social omnivores such as rats and humans, taste is far more than a chemical sense activated by food. By virtue of evolutionary and epigenetic elaboration, taste is associated with negative affect, stress vulnerability, responses to psychoactive substances, pain, and social judgment. A crucial gap in this literature, which spans behavior genetics, affective and social neuroscience, and embodied cognition, concerns links between taste and social behavior in rats. Here we show that rats selectively bred for low saccharin intake are subordinate to high-saccharin-consuming rats when they compete in weight-matched dyads for food, a task used to model depression. Statistical and experimental controls suggest that differential resource utilization within dyads is not an artifact of individual-level processes such as apparatus habituation or ingestive motivation. Tail skin temperature measurements showed that LoS rats display larger hyperthermic responses to social interaction after status is established, evidence linking taste, social stress, autonomic reactivity, and depression-like symptoms. Based on regression using early- and late-competition predictors to predict dyadic disparity in final competition scores, we tentatively suggest that HiS rats emerge as dominant both because of an “early surge” on their part and because LoS acquiesce later. These findings should invigorate the comparative study of individual differences in social status and its relationship to mental and physical health.

The Role of Oxytocin, Vasopressin, and D-Cycloserine in Remediating Social Behavior in Rats with Amygdala Lesions

Autism is a common neurodevelopmental disorder that affects communication and social behavior. To reduce the social deficits characteristic of autism, the compounds oxytocin, arginine vasopressin, D-cycloserine, and D-cycloserine + oxytocin were explored as therapeutic agents. Twenty-one Long Evans Hooded rats underwent a bilateral amygdala lesion, which reduced the time of social interactions between the pairs of animals. Upon administration of D-cycloserine, the social deficits induced by the lesions were significantly reversed in both sexes. In addition, it was observed that the efficacy of the treatments was affected by the sex of the subjects. Male rats had the largest increase in social behavior when given D-cycloserine. However, female rats experienced the largest reduction in social impairment when administered oxytocin. Thus, sexually dimorphic treatments should be further investigated for individuals with autism spectrum disorders.

Administration of kynurenine during adolescence, but not during adulthood, impairs social behavior in rats

Kynurenic acid (KYNA) is a tryptophan metabolite that is present at high concentrations in the brains of persons with schizophrenia. This study tested the hypothesis that treatment with l-kynurenine (L-KYN), which increases KYNA concentration, would produce deficits in social behavior similar to those associated with schizophrenia. Rats treated with L-KYN throughout adolescence exhibited decreased social interaction when tested drug-free as adults. In contrast, neither acute nor chronic treatment during adulthood affected social behavior. These findings demonstrate that increases in KYNA concentration produce deficits in social behavior and that the adolescent brain is particularly susceptible to the effects of high KYNA concentration.

Aging-related changes in the effects of social isolation on social behavior in rats

Aging is generally associated with cognitive dysfunction and alterations in emotional response. Moreover, in social situations, aging decreases social interaction with unfamiliar individuals, suggesting the decline of social cognition/motivation and a high level of anxiety. Although it is known that isolation housing has various effects on subsequent behavior, including social interaction depending on the age at isolation, the effects of isolation on aged subjects have not been examined. In the present study, we investigated the effects of aging and different periods of isolation housing on social interaction in male F344/N rats. Young (3-4months old) and aged (24-25months old) rats were either group-housed or socially isolated for 2 or 4weeks. The rats were tested with age-matched and group-housed unfamiliar males in a social interaction test, and social (e.g. approach/following and sniffing) and non-social behaviors (e.g. self-grooming and ambulation) were recorded. The results indicated that group-housed aged rats showed less approach/following, sniffing, and ambulation than group-housed young rats. Moreover, in young rats, isolation housing gradually increased approach/following and sniffing depending on the isolation period. In contrast, in aged rats, more prolonged isolation (4weeks) attenuated the 2-week isolation-induced increase of sniffing behavior and had no effect on approach/following. The present study suggests that aging decreases social investigation and induces high emotional response to a novel social environment, and that the behaviors can be differentially affected by social isolation depending on the age at isolation and the period of isolation.

Perinatal exposure to polychlorinated biphenyls alters social behaviors in rats

Perinatal exposure to polychlorinated biphenyls (PCBs) leads to significant alterations of neural and hormonal systems. These alterations have been shown to impair motor and sensory development. Less is known about the influence of PCB exposure on developing emotional and motivational systems involved in social interactions and social learning. The present study examined the impact of perinatal PCB exposure (mixture of congeners 47 and 77) on social recognition in juvenile animals, conspecific-directed investigation in adults and on neural and hormonal systems involved in social functions. We used a standard habituation–dishabituation paradigm to evaluate juvenile recognition and a social port paradigm to monitor adult social investigation. Areal measures of the periventricular nucleus (PVN) of the hypothalamus were obtained to provide correlations with related hormone and brain systems. PCB exposed rats were significantly impaired in social recognition as indicated by persistent conspecific-directed exploration by juvenile animals regardless of social experience. As adults, PCB exposure led to a dampening of the isolation-induced enhancement of social investigation. There was not a concomitant alteration of social investigation in pair-housed PCB exposed animals at this stage of development. Interestingly, PVN area was significantly decreased in juvenile animals exposed to PCB during the perinatal period. Shifts in hypothalamic regulation of hormones involved in social behavior and stress could be involved in the behavioral changes observed. Overall, the results suggest that PCB exposure impairs context or experience-dependent modulation of social approach and investigation. These types of social-context deficits are similar to behavioral deficits observed in social disorders such as autism and other pervasive developmental disorders.

Residual social, memory and oxytocin-related changes in rats following repeated exposure to γ-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination

There has been little investigation of the possible lasting adverse effects of γ-hydroxybutyrate (GHB). This study aims to study whether GHB produces residual adverse effects on memory and social behaviour in rats and lasting changes in brain monoamines and oxytocin-related gene expression. Rats received daily intraperitoneal injections of GHB (500 mg/kg), methylenedioxymethamphetamine (MDMA; 5 mg/kg) or their combination (GHB/MDMA) over ten consecutive days. Locomotor activity and body weight were assessed during the dosing period and withdrawal-related anxiety was assessed 24 h after drug cessation. After a washout of 4 weeks, rats were tested on the emergence, social interaction, and object recognition tasks over a 2-week period. Monoamine levels in cortex and striatum, and hypothalamic oxytocin and oxytocin receptor mRNA, were then assessed. MDMA and GHB/MDMA caused modest sensitization of locomotor activity over time, while sedative effects of GHB diminished with repeated exposure. GHB-treated rats showed reduced social interaction 24 h after the final dose, indicating GHB withdrawal-induced anxiety. All drug-treated groups displayed residual deficits in social interaction and object recognition. No changes in monoamine levels were detected 8 weeks post-drug. However, MDMA pre-exposure increased hypothalamic oxytocin mRNA while GHB pre-exposure upregulated oxytocin receptor mRNA. GHB/MDMA pre-exposure caused intermediate changes in both of these measures. GHB treatment caused residual impairments in memory and social behaviour and increases in anxiety, paralleling the lasting adverse effects of MDMA. Both drugs caused lasting neuroadaptations in brain oxytocin systems and this may be related to the long-term social interaction deficiencies caused by both drugs.

Sickness-related odor communication signals as determinants of social behavior in rat: A role for inflammatory processes

Infected animals are avoided by conspecifics, suggesting that the inflammatory cascade may play a significant role in odor communication. Injection of male rats with the bacterial mimetic, lipopolysaccharide (LPS, 100 μg/kg, i.p.), decreased investigation through a wire-mesh partition between healthy male partners. This avoidance response was observed in adult males in response to soiled bedding collected from sick rats, regardless of whether LPS was injected peripherally (100 μg/kg, i.p.) or centrally (0.25 or 2.5 μg, icv). The release of sickness-related odor cues was dose-dependently blocked by icv infusion of the anti-inflammatory cytokine, interleukin-10 (IL-10; 20 or 200 ng), and reproduced by icv infusion of pro-inflammatory cytokine, IL-1β (5 or 50 ng). Subcutaneous pretreatment with either estradiol benzoate (20 μg/kg) or testosterone propionate (50 or 500 μg/kg) to adult males that were administered LPS inhibited release of aversive odor cues, but these hormones alone did not influence odor properties. Importantly, the avoidance response to sickness-related odor was not associated with changes in plasma corticosterone, testosterone, or IL-6 levels of odor donors. However, plasma IL-1β concentrations of sick animals was in fact predictive of aversive responses in conspecifics, suggesting that the inflammatory cascade, but not plasma steroid hormones, is likely to mediate aversive properties in odor that functions to signal illness state to conspecifics.

Phencyclidine affects firing activity of ventral tegmental area neurons related to both reward and social behaviors in rats

Phencyclidine affects firing activity of ventral tegmental area neurons related to both reward and social behaviors in rats

Phencyclidine affects firing activity of basolateral amygdala neurons related to social behavior in rats

Negative symptoms of schizophrenia, such as social withdrawal and blunted affect, usually persist for a long period, making rehabilitation difficult. Many studies have demonstrated a close relationship between function of the amygdala and social behavior. Normal social behavior is disturbed in animals administered phencyclidine (PCP), which is now considered a reliable pharmacological model of schizophrenia. Recent studies have reported that disruption of social behavior in PCP-treated rats involved dysfunction of the amygdala. Disturbance of function of the amygdala has also been reported in schizophrenic patients. However, no study has yet examined the effects of PCP on the firing activity of amygdala neurons. In the present study, we recorded the unit activity of basolateral amygdala neurons while rats engaged in socially interactive behavior. After identifying the response properties of recorded neurons, we then recorded the same neurons with systemic PCP administration. Approximately half of the neurons recorded from exhibited an increase in spontaneous discharge rate during social interaction. Only a few neurons exhibited suppression of discharge rate during social interaction. Systemic administration of PCP induced long-lasting activation in half of the neurons that exhibited an increase in firing rate during social interaction. PCP activated half of basolateral amygdala neurons related to socially interactive behavior, and might in this fashion produce dysfunction of social behavior.