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Positive social interactions are essential for emotional well-being, healthy development, establishment and maintenance of adequate social structures and reproductive success of humans and animals. Here, we review the studies that have investigated whether forms of social interaction that occur in different phases of the lifespan of animals, i.e., maternal behavior, social play and sexual interaction are rewarding in rodents and non-human primates. We show that these three forms of social interaction can be used as incentive for place conditioning, lever pressing and maze learning, three setups that have been extensively used to study the rewarding properties of food and drugs of abuse and their neural underpinnings. The experience of positive social interactions during key developmental ages has profound and long-lasting effects on brain function and behavior in emotional, motivational and cognitive domains. For instance, pup interaction is more rewarding than cocaine for early postpartum dams and rats deprived of the opportunity to play during adolescence show social and cognitive impairments at adulthood. Furthermore, sexual behavior is only overtly rewarding when animals can control the rate at which the sexual interaction occurs. Last, we discuss how animal models contributed to our understanding of social reward mechanisms and its psychological components throughout development.

Social rewards are fundamental to survival and overall health. Several studies suggest that adequate social stimuli during early life are critical for developing appropriate socioemotional and cognitive skills, whereas adverse social experiences negatively affect the proper development of brain and behavior, by increasing the susceptibility to develop neuropsychiatric conditions. Therefore, a better understanding of the neural mechanisms underlying social interactions, and their rewarding components in particular, is an important challenge of current neuroscience research. In this context, preclinical research has a crucial role: Animal models allow to investigate the neurobiological aspects of social reward in order to shed light on possible neurochemical alterations causing aberrant social reward processing in neuropsychiatric diseases, and they allow to test the validity and safety of innovative therapeutic strategies. Here, we discuss preclinical research that has investigated the rewarding properties of two forms of social interaction that occur in different phases of the lifespan of mammals, that is, mother–infant interaction and social interactions with peers, by focusing on the main neurotransmitter systems mediating their rewarding components. Together, the research performed so far helped to elucidate the mechanisms of social reward and its psychobiological components throughout development, thus increasing our understanding of the neurobiological substrates sustaining social functioning in health conditions and social dysfunction in major psychiatric disorders. (Figure presented.).

Background and objective: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder for which no treatments exist. Fragile X syndrome (FXS) is the most common form of inherited mental retardation and the most frequent monogenic cause of ASD. Given the lack of pharmacological treatments for ASD, increasing interest is devoted to non-pharmacological approaches, including dietary interventions. Omega-3 polyunsaturated fatty acids (PUFAs) are critical for neurobehavioraldevelopment. This study had two aims: 1. To validatethe recently developed Fmr1-Δexon 8 rat model of FXS; 2. To assess the impact of omega-3 PUFAs dietary supplementation during pregnancy and lactation on the altered behavior displayed by Fmr1-Δexon 8 rats. Methods: Female Fmr1-Δexon 8 and wild-type Sprague–Dawley rats were fed with either an omega-3 PUFAs enriched diet or with an isocaloric control diet during pregnancy and lactation. Behavioral experiments were carried out on the infant (Postnatal days (PNDs) 9 and 13), juvenile (PND 35) and adult (PND 90) male offspring. Results:Fmr1-Δexon 8 pups showed hypolocomotion, reduced ultrasonic vocalizations (USVs) emission and impaired social discrimination compared to wild-type controls. Juvenile and adult Fmr1-Δexon 8 rats showed deficits in the social and cognitive domains, that were counteracted by perinatal omega-3 PUFAs supplementation. Conclusion: Our results support the validity of the Fmr1-Δexon 8 rat model to mimic key autistic-like features and support an important role of omega-3 PUFAs during of neurodevelopment. Although the mechanisms underlying the beneficial effects of omega-3 PUFAs supplementation in ASD needs to be clarified, this dietary intervention holds promise to mitigate core and comorbid autistic features.

Background:Human serum albumin (HSA), the most abundant protein in plasma, is a monomeric multi-domain macromolecule with at least nine binding sites for endogenous and exogenous ligands. HSA displays an extraordinary ligand binding capacity as a depot and carrier for many compounds including most acidic drugs. Consequently, HSA has the potential to influence the pharmacokinetics and pharmacodynamics of drugs.Objective:In this review, the structural determinants of drug binding to the multiple sites of HSA are analyzed and discussed in detail. Moreover, insight into the allosteric and competitive mechanisms underpinning drug recognition, delivery, and efficacy are analyzed and discussed.Conclusion:As several factors can modulate drug binding to HSA (e.g., concurrent administration of drugs competing for the same binding site, ligand binding to allosteric-coupled clefts, genetic inherited diseases, and post-translational modifications), ligand binding to HSA is relevant not only under physiological conditions, but also in the pharmacological therapy management.

Methylenedioxypyrovalerone (MDPV) is the most popular synthetic cathinone found in products marketed as 'bath salts', widely abused among teenagers and young adults. Synthetic cathinones have pharmacological effects resembling those of psychostimulants, which are known to disrupt a variety of social behaviors. However, despite the popular use of MDPV by young people in social contexts, information about its effects on social behavior is scarce. To investigate the impact of MDPV on social behavior at young age, and the underlying neurobehavioral mechanisms, we focused on social play behavior. Social play behavior is the most characteristic social behavior displayed by young mammals and it is crucial for neurobehavioral development. Treatment with MDPV reduced social play behavior in both juvenile and young adult male rats, and its play-suppressant effect was subject to tolerance but not sensitization. As the behavioral effects of MDPV have been ascribed to dopaminergic and noradrenergic neurotransmission, and given the role of these neurotransmitters in social play, we investigated the involvement of dopamine and noradrenaline in the play-suppressant effects of MDPV. The effects of MDPV on social play were blocked by either the α2 adrenoceptor antagonist RX821002 or the dopamine receptor antagonist flupenthixol, given alone or together at sub-effective doses. In sum, MDPV selectively suppresses the most vigorous social behavior of developing rats through both noradrenergic and dopaminergic mechanisms. This study provides important preclinical evidence of the deleterious effects of MDPV on social behavior, and as such increases our understanding of the neurobehavioral effects of this popular cathinone.

Objective: We were aimed at evaluating the long-term impact of perinatal an omega-3 fatty acid-enriched diet on the mevalonate/cholesterol pathway in the brain of male offspring. Methods: Female rats were fed with standard or omega-3 fatty acid-enriched diet during pregnancy and lactation. Liver, brain and plasma were collected from infant, adolescent and adult male offspring for subsequent biochemical and morphological analyses. Results: The omega-3 enriched diet induced region-dependent changes of the 3-hydroxy 3-methylglutaryl Coenzyme A reductase in the brain and affected notably RhoA/CREB signaling and the nerve growth factor content in the hippocampus. Our data reveal a long-lasting impact of perinatal omega-3 fatty acid supplementation on hippocampal nerve growth factor levels mediated by reduced 3-hydroxy 3-methylglutaryl Coenzyme A reductase activation state and enhanced CREB signaling. Discussion: These data underline the importance of the perinatal omega-3 enriched diet for adult brain function and reveal a new pathway important for nerve growth factor regulation.

International audience; Cannabis exposure during the perinatal period results in varied and significant consequences in affected offspring. The prevalence of detrimental outcomes of perinatal cannabis exposure is likely to increase in tandem with the broadening of legalization and acceptance of the drug. As such, it is crucial to highlight the immediate and protracted consequences of cannabis exposure on pre-and post-natal development. Here, we identify lasting changes in neurons' learning flexibility (synaptic plasticity) and epigenetic misregulation in animal models of perinatal cannabinoid exposure (using synthetic cannabinoids or active components of the cannabis plant) in addition to significant alterations in social behavior and executive functions. These findings are supported by epidemiological data indicating similar behavioral outcomes throughout life in human offspring exposed to cannabis during pregnancy. Further, we indicate important lingering questions regarding accurate modeling of perinatal cannabis exposure as well as the need for sex-and agedependent outcome measures in future studies.