Social Conditioned Place Preference Research Articles

Conditioned preferences: Gated by experience, context, and endocrine systems

Central to the navigation of an ever-changing environment is the ability to form positive associations with places and conspecifics. The functions of location and social conditioned preferences are often studied independently, limiting our understanding of their interplay. Furthermore, a de-emphasis on natural functions of conditioned preferences has led to neurobiological interpretations separated from ecological context. By adopting a naturalistic and ethological perspective, we uncover complexities underlying the expression of conditioned preferences. Development of conditioned preferences is a combination of motivation, reward, associative learning, and context, including for social and spatial environments. Both social- and location-dependent reward-responsive behaviors and their conditioning rely on internal state-gating mechanisms that include neuroendocrine and hormone systems such as opioids, dopamine, testosterone, estradiol, and oxytocin. Such reinforced behavior emerges from mechanisms integrating past experience and current social and environmental conditions. Moreover, social context, environmental stimuli, and internal state gate and modulate motivation and learning via associative reward, shaping the conditioning process. We highlight research incorporating these concepts, focusing on the integration of social neuroendocrine mechanisms and behavioral conditioning. We explore three paradigms: 1) conditioned place preference, 2) conditioned social preference, and 3) social conditioned place preference. We highlight nonclassical species to emphasize the naturalistic applications of these conditioned preferences. To fully appreciate the complex integration of spatial and social information, future research must identify neural networks where endocrine systems exert influence on such behaviors. Such research promises to provide valuable insights into conditioned preferences within a broader naturalistic context.

Differential contribution of canonical and noncanonical NLGN3 pathways to early social development and memory performance

Neuroligin (NLGN) 3 is a postsynaptic cell adhesion protein organizing synapse formation through two different types of transsynaptic interactions, canonical interaction with neurexins (NRXNs) and a recently identified noncanonical interaction with protein tyrosine phosphatase (PTP) δ. Although, NLGN3 gene is known as a risk gene for neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID), the pathogenic contribution of the canonical NLGN3-NRXN and noncanonical NLGN3-PTPδ pathways to these disorders remains elusive. In this study, we utilized Nlgn3 mutant mice selectively lacking the interaction with either NRXNs or PTPδ and investigated their social and memory performance. Neither Nlgn3 mutants showed any social cognitive deficiency in the social novelty recognition test. However, the Nlgn3 mutant mice lacking the PTPδ pathway exhibited significant decline in the social conditioned place preference (sCPP) at the juvenile stage, suggesting the involvement of the NLGN3-PTPδ pathway in the regulation of social motivation and reward. In terms of learning and memory, disrupting the canonical NRXN pathway attenuated contextual fear conditioning while disrupting the noncanonical NLGN3-PTPδ pathway enhanced it. Furthermore, disruption of the NLGN3-PTPδ pathway negatively affected the remote spatial reference memory in the Barnes maze test. These findings highlight the differential contributions of the canonical NLGN3-NRXN and noncanonical NLGN3-PTPδ synaptogenic pathways to the regulation of higher order brain functions associated with ASD and ID.

Social Interaction Is Less Rewarding in Adult Female than in Male Mice.

(1) Background: Positive social relationships are essential for mental and physical health. However, not all individuals experience social interaction as a rewarding activity. (2) Methods: Social interaction reward in mice can be assessed by social conditioned place preference (CPP). The aim of this study is to investigate sex-dependent differences in the neurological underpinnings underlying social versus non-social phenotypes, using adult male and female C57BL/6J mice. (3) Results: Adult female mice expressed significantly less social reward than males from the same strain. Accordingly, pairs of male mice spent more time interacting as compared to female pairs. Subsequently, we analyzed neuropeptides previously reported to be important regulators of social behavior such as oxytocin, vasopressin, and orexin, in addition to Ca2+/calmodulin-dependent protein kinase II (αCaMKII), shown to be involved in social reward. Levels of neuropeptides and αCaMKII were comparable between males and females in all investigated regions. Yet, a significant negative correlation was found between endogenous oxytocin expression and social reward in female pairs. (4) Conclusions: Sex differences in the prevalence of many mental health disorders might at least in part be due to sex differences in social reward. Therefore, more research is needed to unravel the candidate(s) underlying this behavioral difference.

Alterations in the social-conditioned place preference and density of dopaminergic neurons in the ventral tegmental area in Clsnt2-KO mice.

The incidence of autistic spectrum disorders (ASD) constantly increases in the world. Studying the mechanisms underlying ASD as well as searching for new therapeutic targets are crucial tasks. Many researchers agree that autism is a neurodevelopmental disorder. Clstn2-KO mouse strain with a knockout of calsyntenin 2 gene (Clstn2) is model for investigating ASD. This study aims to evaluate the social-conditioned place preference as well as density of dopaminergic (DA) neurons in the ventral tegmental area (VTA), which belongs to the brain reward system, in the males of the Clstn2-KO strain using wild type C57BL/6J males as controls. Social-conditioned place preference test evaluates a reward-dependent component of social behavior. The results of this test revealed differences between the Clstn2-KO and the control males, as the former did not value socializing with the familiar partner, spending equal time in the isolation- and socializing-associated compartments. The Clstn2-KO group entered both compartments more frequently, but spent less time in the socializing-associated compartment compared to the controls. By contrast, the control males of the C57BL/6J strain spent more time in socializing-associated compartment and less time in the compartment that was associated with loneness. At the same time, an increased number of DA and possibly GABA neurons labeled with antibodies against the type 2 dopamine receptor as well as against tyrosine hydroxylase were detected in the VTA of the Clstn2-KO mice. Thus, a change in social-conditioned place preference in Clstn2-KO mice as well as a higher number of neurons expressing type 2 dopamine receptors and tyrosine hydroxylase in the VTA, the key structure of the mesolimbic dopaminergic pathway, were observed.

The mu opioid receptor and the orphan receptor GPR151 contribute to social reward in the habenula

The mu opioid receptor (MOR) and the orphan GPR151 receptor are inhibitory G protein coupled receptors that are enriched in the habenula, a small brain region involved in aversion processing, addiction and mood disorders. While MOR expression in the brain is widespread, GPR151 expression is restricted to the habenula. In a previous report, we created conditional ChrnB4-Cre × Oprm1fl/fl (so-called B4MOR) mice, where MORs are deleted specifically in Chrnb4-positive neurons restricted to the habenula, and shown a role for these receptors in naloxone aversion. Here we characterized the implication of habenular MORs in social behaviors. B4MOR−/− mice and B4MOR+/+ mice were compared in several social behavior measures, including the chronic social stress defeat (CSDS) paradigm, the social preference (SP) test and social conditioned place preference (sCPP). In the CSDS, B4MOR−/− mice showed lower preference for the social target (unfamiliar mouse of a different strain) at baseline, providing a first indication of deficient social interactions in mice lacking habenular MORs. In the SP test, B4MOR−/− mice further showed reduced sociability for an unfamiliar conspecific mouse. In the sCPP, B4MOR−/− mice also showed impaired place preference for their previous familiar littermates after social isolation. We next created and tested Gpr151−/− mice in the SP test, and also found reduced social preference compared to Gpr151+/+ mice. Altogether our results support the underexplored notion that the habenula regulates social behaviors. Also, our data suggest that the inhibitory habenular MOR and GPR151 receptors normally promote social reward, possibly by dampening the aversive habenula activity.

A virtual reality social conditioned place preference paradigm for humans: Does trait social anxiety affect approach and avoidance of virtual agents?

Approach and avoidance of positive and negative social cues are fundamental to prevent isolation and ensure survival. High trait social anxiety is characterized by an avoidance of social situations and extensive avoidance is a risk factor for the development of social anxiety disorder (SAD). Therefore, experimental methods to assess social avoidance behavior in humans are essential. The social conditioned place preference (SCPP) paradigm is a well-established experimental paradigm in animal research that is used to objectively investigate social approach–avoidance mechanisms. We retranslated this paradigm for human research using virtual reality. To this end, 58 healthy adults were exposed to either a happy- or angry-looking virtual agent in a specific room, and the effects of this encounter on dwell time as well as evaluation of this room in a later test without an agent were examined. We did not observe a general SCPP effect on dwell time or ratings but discovered a moderation by trait social anxiety, in which participants with higher trait social anxiety spent less time in the room in which the angry agent was present before, suggesting that higher levels of trait social anxiety foster conditioned social avoidance. However, further studies are needed to verify this observation and substantiate an association with social anxiety disorder. We discussed the strengths, limitations, and technical implications of our paradigm for future investigations to more comprehensively understand the mechanisms involved in social anxiety and facilitate the development of new personalized treatment approaches by using virtual reality.

Leptin enhances social motivation and reverses chronic unpredictable stress-induced social anhedonia during adolescence

Social anhedonia, a loss of interest and pleasure in social interactions, is a common symptom of major depression as well as other psychiatric disorders. Depression can occur at any age, but typically emerges in adolescence or early adulthood, which represents a sensitive period for social interaction that is vulnerable to stress. In this study, we evaluated social interaction reward using a conditioned place preference (CPP) paradigm in adolescent male and female mice. Adolescent mice of both sexes exhibited a preference for the social interaction-associated context. Chronic unpredictable stress (CUS) impaired the development of CPP for social interaction, mimicking social anhedonia in depressed adolescents. Conversely, administration of leptin, an adipocyte-derived hormone, enhanced social interaction-induced CPP in non-stressed control mice and reversed social anhedonia in CUS mice. By dissecting the motivational processes of social CPP into social approach and isolation avoidance components, we demonstrated that leptin treatment increased isolation aversion without overt social reward effect. Further mechanistic exploration revealed that leptin stimulated oxytocin gene transcription in the paraventricular nucleus of the hypothalamus, while oxytocin receptor blockade abolished the leptin-induced enhancement of socially-induced CPP. These results establish that chronic unpredictable stress can be used to study social anhedonia in adolescent mice and provide evidence that leptin modulates social motivation possibly via increasing oxytocin synthesis and oxytocin receptor activation.

Establishment of a social conditioned place preference paradigm for the study of social reward in female mice

Social interactions can be and often are rewarding. The effect of social contact strongly depends on circumstances, and the reward may be driven by varied motivational processes, ranging from parental or affiliative behaviors to investigation or aggression. Reward associated with nonreproductive interactions in rodents is measured using the social conditioned place preference (sCPP) paradigm, where a change in preference for an initially neutral context confirms reinforcing effects of social contact. Here, we revised the sCPP method and reexamined social reward in adult female mice. Contrary to earlier studies, we found that robust rewarding effects of social contact could be detected in adult (14-week-old) female C57BL/6 mice when the sCPP task was refined to remove confounding factors. Strikingly, the rewarding effects of social interaction were only observed among female siblings who remained together from birth. Contact with same-age nonsiblings was not rewarding even after 8 weeks of cohousing. Other factors critical for the social reward effect in the sCPP paradigm included the number of conditioning sessions and the inherent preference for contextual cues. Thus, we show that social interaction is rewarding in adult female mice, but this effect strictly depends on the familiarity of the interaction partners. Furthermore, by identifying confounding factors, we provide a behavioral model to study the mechanisms underlying the rewarding effects of nonreproductive social interaction in adult mice.

Waving Through the Window: A Model of Volitional Social Interaction in Female Mice

BackgroundMouse models of social behavior fail to account for volitional aspects of social interaction, and current neurobiological investigation of social behavior is performed almost exclusively using C57BL/6J mice, the background strain of most transgenic mice. Here, we introduce a mouse model of operant social self-administration and choice, using a custom-made apparatus. MethodsFirst, we trained adolescent and adult female C57BL/6J and CD1 mice to self-administer palatable food pellets and then to lever press under increasing fixed-ratio response requirements for access to an age-matched female social partner. Next, we tested their motivation to seek social interaction using a progressive ratio reinforcement schedule, relapse to social seeking after social isolation, and choice between palatable food versus social interaction. We also tested social conditioned place preference in adult female CD1 and C57BL/6J mice. ResultsAdolescent and adult female mice of both strains showed similar rates of food self-administration. In contrast, CD1 mice demonstrated significantly stronger social self-administration than C57BL/6J mice under both reinforcement schedules. CD1 but not C57BL/6J mice demonstrated robust social seeking after social isolation. In the choice task, CD1 mice preferred social interaction, whereas C57BL/6J mice preferred food. CD1 but not C57BL/6J mice demonstrated robust social conditioned place preference. The strain differences were age independent. ConclusionsOur data show that CD1 mice are a better strain for studying female social reward learning. Our mouse operant social model provides a tool for research on neurobiological substrates of female social reward and disruption of social reward in psychiatric disorders using mouse-specific genetic tools.

μ-Opioid Receptor (Oprm1) Copy Number Influences Nucleus Accumbens Microcircuitry and Reciprocal Social Behaviors.

The μ-opioid receptor regulates reward derived from both drug use and natural experiences, including social interaction, through actions in the nucleus accumbens. Here, we studied nucleus accumbens microcircuitry and social behavior in male and female mice with heterozygous genetic knockout of the μ-opioid receptor (Oprm1+/-). This genetic condition models the partial reduction of μ-opioid receptor signaling reported in several neuropsychiatric disorders. We first analyzed inhibitory synapses in the nucleus accumbens, using methods that differentiate between medium spiny neurons (MSNs) expressing the D1 or D2 dopamine receptor. Inhibitory synaptic transmission was increased in D2-MSNs of male mutants, but not female mutants, while the expression of gephyrin mRNA and the density of inhibitory synaptic puncta at the cell body of D2-MSNs was increased in mutants of both sexes. Some of these changes were more robust in Oprm1+/- mutants than Oprm1-/- mutants, demonstrating that partial reductions of μ-opioid signaling can have large effects. At the behavioral level, social conditioned place preference and reciprocal social interaction were diminished in Oprm1+/- and Oprm1-/- mutants of both sexes. Interaction with Oprm1 mutants also altered the social behavior of wild-type test partners. We corroborated this latter result using a social preference task, in which wild-type mice preferred interactions with another typical mouse over Oprm1 mutants. Surprisingly, Oprm1-/- mice preferred interactions with other Oprm1-/- mutants, although these interactions did not produce a conditioned place preference. Our results support a role for partial dysregulation of μ-opioid signaling in social deficits associated with neuropsychiatric conditions.SIGNIFICANCE STATEMENT Activation of the μ-opioid receptor plays a key role in the expression of normal social behaviors. In this study, we examined brain function and social behavior of female and male mice, with either partial or complete genetic deletion of μ-opioid receptor expression. We observed abnormal social behavior following both genetic manipulations, as well as changes in the structure and function of synaptic input to a specific population of neurons in the nucleus accumbens, which is an important brain region for social behavior. Synaptic changes were most robust when μ-opioid receptor expression was only partially lost, indicating that small reductions in μ-opioid receptor signaling can have a large impact on brain function and behavior.

Parametric investigation of social place preference in adolescent mice.

Social interaction promotes survival by helping animals to form stable and supportive groups. Additionally, maladaptive social behavior is a hallmark of disorders such as autism and schizophrenia. In many different animal species, including humans, social interaction can be inherently rewarding. Lately there has been growing interest in studying the neurobiological underpinnings of social interaction and learned social behavior in rodent behavioral models. One common procedure is conditioned place preference (CPP) to measure the rewarding effects of social interaction and social reward learning. Social CPP was originally used in rats but has been adapted recently for use in mice, enabling use of the vast array of genetic tools available in mice. Here we studied the role of age, sex, bedding, and prior social isolation on the expression of social CPP in male and female mice. We found that without social deprivation male mice display moderate and temporary social CPP during early adolescence but not adulthood. Early life social isolation increased social CPP in female but not male mice. In contrast, cocaine CPP was robust and long-lasting in male and female mice. Our results demonstrate that social CPP in mice is variable, occurring under only specific conditions, and that social isolation promotes social reward in female but not male mice. We discuss potential methodological and interpretive issues of the mouse social CPP model. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Range use is related to free-range broiler chickens’ behavioral responses during food and social conditioned place preference tests

Free-range broiler chickens usually show an uneven spatial utilization of an outdoor range. Due to behavioral and cognitive between-individual differences, some animals may be driven to associate food and conspecifics more strongly to the barn, causing them to be less prone to explore the range. In this study, we aimed to understand how broiler chickens with different ranging levels (low- and high-ranging chickens) would behave under conditioned place preference (CPP) test situations. We used two cohorts conditioned to two natural rewarding stimuli: food and social companions. In a two-chambered apparatus, one cohort (n = 31, 16 high-ranging, and 15 low-ranging chickens) was conditioned to one chamber that always contained a cup with a food reward (mealworms), while the cup in the other chamber was always empty. The same design was also used with the second cohort (n = 31, 15 high-ranging and 16 low-ranging chickens), although instead of food, the reward was the physical presence of two conspecifics. During the testing trials, the animals had access to both empty chambers, and the time spent in each chamber was quantified. For the first day of the food CPP test, both the high- and low-ranging chickens spent significantly more time in the conditioned chamber, where they had previously found mealworms. During the following extinction days, the animals showed a gradual loss of their learned preference, increasing their immobility in the apparatus. High-ranging chickens were more immobile than low-ranging chickens, however, as their number of trials without moving was significantly higher. Unexpectedly, during the first day of the social CPP test, only high-ranging chickens showed a place preference. An overall place preference was observed only on the second day, with no chamber preference during the extinction days. Our results suggest that whether and how a stimulus-reward association occurs for free-range chickens may also be dependent on individual differences and the nature of the reward (food or social). Since associative learning occurs on a daily basis for farmed animals and the way individuals learn or value the reward varies, this research advanced our knowledge of animal behavior and individual cognitive differences that can be highly beneficial in improving animals’ living conditions; this new understanding will allow for a more individualized approach to rearing broiler chickens in outdoor systems.

Adapting social conditioned place preference for use in young children.

Social-emotional processing is key to daily interactions and routines, yet a challenging construct to quantify. Measuring social and emotional processing in young children, children with language impairments, or non-verbal children, presents additional challenges. This study addresses a pressing need for tools to probe internal responses such as feelings, drives, and motivations that do not rely on intact language skills. In this study, we extend our recent success of inducing conditioned place preference (CPP) in children to demonstrate the success of using a social unconditioned stimulus in the CPP paradigm in both typically developing children (n=36) and in children with a diagnosis of autism spectrum disorder (n=14). This is the first study to demonstrate successful social conditioned place preference in the human population. Both typically developing children and children with autism spectrum disorder demonstrate significant social conditioned place preference by spending significantly more time in the room paired with social interaction following training. Significant heterogeneity of CPP scores in both groups of children indicates that social motivation is expressed along a continuum, and that the CPP paradigm may provide a more comprehensive characterization of social motivation beyond a diagnosis of an autism spectrum disorder for each child.

Individual variation in the attribution of incentive salience to social cues

Research on the attribution of incentive salience to drug cues has furthered our understanding of drug self-administration in animals and addiction in humans. The influence of social cues on drug-seeking behavior has garnered attention recently, but few studies have investigated how social cues gain incentive-motivational value. In the present study, a Pavlovian conditioned approach (PCA) procedure was used to identify rats that are more (sign-trackers; STs) or less (goal-trackers; GTs) prone to attribute incentive salience to food reward cues. In Experiment 1, a novel procedure employed social ‘peers’ to compare the tendency of STs and GTs to attribute incentive salience to social reward cues as well as form a social-conditioned place preference. In Experiment 2, social behavior of STs and GTs was compared using social interaction and choice tests. Finally, in Experiment 3, levels of plasma oxytocin were measured in STs and GTs seven days after the last PCA training session, because oxytocin is known to modulate the mesolimbic reward system and social behavior. Compared to GTs, STs attributed more incentive salience to social-related cues and exhibited prosocial behaviors (e.g., social-conditioned place preference, increased social interaction, and social novelty-seeking). No group differences were observed in plasma oxytocin levels. Taken together, these experiments demonstrate individual variation in the attribution of incentive salience to both food- and social-related cues, which has important implications for the pathophysiology of addiction.

Social interaction reward in rats has anti-stress effects.

Social interaction in an alternative context can be beneficial against drugs of abuse. Stress is known to be a risk factor that can exacerbate the effects of addictive drugs. In this study, we investigated whether the positive effects of social interaction are mediated through a decrease in stress levels. For that purpose, rats were trained to express cocaine or social interaction conditioned place preference (CPP). Behavioural, hormonal, and molecular stress markers were evaluated. We found that social CPP decreased the percentage of incorrect transitions of grooming and corticosterone to the level of naïve untreated rats. In addition, corticotropin‐releasing factor (CRF) was increased in the bed nucleus of stria terminalis after cocaine CPP. In order to study the modulation of social CPP by the CRF system, rats received intracerebroventricular CRF or alpha‐helical CRF, a nonselective antagonist of CRF receptors. The subsequent effects on CPP to cocaine or social interaction were observed. CRF injections increased cocaine CPP, whereas alpha‐helical CRF injections decreased cocaine CPP. However, alpha‐helical CRF injections potentiated social CPP. When social interaction was made available in an alternative context, CRF‐induced increase of cocaine preference was reversed completely to the level of rats receiving cocaine paired with alpha‐helical CRF. This reversal of cocaine preference was also paralleled by a reversal in CRF‐induced increase of p38 MAPK expression in the nucleus accumbens shell. These findings suggest that social interaction could contribute as a valuable component in treatment of substance use disorders by reducing stress levels.

Impaired innate and conditioned social behavior in adult C57Bl6/J mice prenatally exposed to chlorpyrifos

BackgroundSigns of pervasive developmental disorder and social deficits were reported in toddlers and children whose mothers were exposed to organophosphate pesticides during pregnancy. Deficits in social preference were reported in adult male mice exposed to chlorpyrifos on gestational days 12–15. This study aimed (a) to test the hypothesis that adult female and male mice that were exposed prenatally to subtoxic doses of chlorpyrifos would be impaired in social behavior and (b) to determine if prenatal chlorpyrifos altered the expression of transcripts for oxytocin in the hypothalamus. Pregnant mice were treated by gavage with corn oil vehicle or 2.5 mg/kg or 5 mg/kg of CPF on gestational days 12–15. Social preference, social and non-social conditioned place preference tasks were tested in adults. Expression of oxytocin transcripts in hypothalamus was measured by qPCR.ResultsChlorpyrifos (5 mg/kg on GD 12–15) reduced the innate preference for a conspecific in a dose and sex dependent manner. Adult males exposed prenatally to 5 mg/kg CPF showed a reduction in social preference. Socially conditioned place preference was impaired in offspring of dams treated with either dose of CPF. Non-social appetitive place conditioning was impaired in offspring of dams exposed to 2.5 mg/kg, but not to 5 mg/kg chlorpyrifos. Prenatal chlorpyrifos treatment did not alter the expression of the oxytocin mRNA in the hypothalamus, although expression was significantly lower in females.ConclusionsPrenatal chlorpyrifos induced innate and learned social deficits and non-specific conditioning deficits in adult mice in a sex-dependent manner. Males showed specific social deficits following the higher dose whereas both males and females showed a more generalized conditioning deficit following the intermediate dose.

SHANK3 Downregulation in the Ventral Tegmental Area Accelerates the Extinction of Contextual Associations Induced by Juvenile Non-familiar Conspecific Interaction.

Haploinsufficiency of the SHANK3 gene, encoding for a scaffolding protein located in the postsynaptic density of glutamatergic synapse, has been linked to forms of autism spectrum disorders (ASDs). It has been shown that SHANK3 controls the maturation of social reward circuits in the ventral tegmental area (VTA). Whether the impairments in associative learning observed in ASD relate to SHANK3 insufficiency restricted to the reward system is still an open question. Here, we first characterize a social-conditioned place preference (CPP) paradigm based on the direct and free interaction with a juvenile and non-familiar conspecific. In both group- and single-housed C57Bl6/j late adolescence male mice, this CPP protocol promotes the formation of social-induced contextual associations that undergo extinction. Interestingly, the downregulation of Shank3 expression in the VTA altered the habituation to a non-familiar conspecific during conditioning and accelerated the extinction of social-induced conditioned responses. Thus, inspired by the literature on drugs of abuse-induced contextual learning, we propose that acquisition and extinction of CPP might be used as behavioral assays to assess social-induced contextual association and “social-seeking” dysfunctions in animal models of psychiatric disorders.

Opioid modulation of social play reward in juvenile rats

Social play behaviour is a vigorous form of social interaction abundant during the juvenile and adolescent phases of life in many mammalian species, including rats and humans. Social play is thought to be important for social, emotional and cognitive development. Being a rewarding activity, the expression of social play depends on its pleasurable and motivational properties. Since opioids have been widely implicated in reward processes, in the present study we investigated the role of opioids in the pleasurable and motivational properties of social play behaviour in rats. To assess social play motivation, an operant conditioning setup was used in which rats responded for social play under a progressive ratio schedule of reinforcement. Treatment with the opioid receptor agonist morphine reduced responding for social play at the highest dose tested, likely due to its rate-limiting effects. Morphine treatment increased the expression of social play behaviour during reinforced periods. The acquisition of social play-induced conditioned place preference (CPP) in a subeffective conditioning protocol was enhanced by treatment with morphine. Morphine treatment alone also induced CPP. In contrast, antagonizing opioid receptors with naloxone reduced responding for social play, the expression of social play and blocked the development of social play-induced CPP. These data implicate opioid neurotransmission in both the pleasurable and the motivational aspects of social play behaviour in rats.This article is part of the Special Issue entitled ‘The neuropharmacology of social behavior: from bench to bedside’.

Developmental exposures to ultrafine particle air pollution reduces early testosterone levels and adult male social novelty preference: Risk for children’s sex-biased neurobehavioral disorders

Epidemiological studies have reported associations of air pollution exposures with various neurodevelopmental disorders such as autism spectrum disorder (ASD), attention deficit and schizophrenia, all of which are male-biased in prevalence. Our studies of early postnatal exposure of mice to the ultrafine particle (UFP) component of air pollution, considered the most reactive component, provide support for these epidemiological associations, demonstrating male-specific or male-biased neuropathological changes and cognitive and impulsivity deficits consistent with these disorders. Since these neurodevelopmental disorders also include altered social behavior and communication, the current study examined the ability of developmental UFP exposure to reproduce these social behavior deficits and to determine whether any observed alterations reflected changes in steroid hormone concentrations. Elevated plus maze, social conditioned place preference, and social novelty preference were examined in adult mice that had been exposed to concentrated (10-20x) ambient UFPs averaging approximately 45 ug/m3 particle mass concentrations from postnatal day (PND) 4–7 and 10–13 for 4 h/day. Changes in serum testosterone (T) and corticosterone where measured at postnatal day (P)14 and approximately P120. UFP exposure decreased serum T concentrations on PND 14 and social nose-to-nose sniff rates with novel males in adulthood, suggesting social communication deficits in unfamiliar social contexts. Decreased sniff rates were not accounted for by alterations in fear-mediated behaviors and occurred without overt deficits in social preference, recognition or communication with a familiar animal or alterations in corticosterone. Adult T serum concentrations were positively correlated with nose to nose sniff rates. Collectively, these studies confirm another feature of male-biased neurodevelopmental disorders following developmental exposures to even very low levels of UFP air pollution that could be related to alterations in sex steroid programming of brain function.

Pavlovian conditioning of social exploration in adult female rats

Social conditioned place preference (SCPP) studies show that the reward value of social interaction is amenable to the laws of associative learning, such that it becomes associated with the physical properties of the context. However, social interaction can be initiated and maintained by a variety of motivations, such as the exploration of a novel conspecific, aggression, mutual grooming and mating-like actions. In order to study whether social exploration is rewarding, we used a conventional Pavlovian conditioning procedure in which access to a restrained same-sex rat served as a reward. Three dependent variables in two experiments showed that the reward value of social exploration becomes conditioned to a transient cue, and it is also subject to extinction and spontaneous recovery. The results may help to elucidate the mixed results obtained with SCPP procedures.