The importance of being social : preclinical studies on social development, cognitive control and drug addiction

Abstract

Marked developmental changes in social behavior take place during youth, including increased complexity of the social repertoire and dramatic increment of peer-directed social interactions. Social experiences early in life are of major importance for proper behavioral development and create valuable practice scenarios for complex social interactions throughout life. Conversely, social insults during development can create a predisposing factor for psychopathology. The overall aim of this thesis is to enhance our understanding of the neurobiology of adolescent social behavior and its importance for behavioral development. Children and young mammals spend a substantial part of maturation engaging in play with peers, such as running, chasing, climbing and play fighting. Social play has been shown to be a natural reinforcer, and neurotransmitter systems implicated in the motivational, pleasurable and cognitive aspects of natural and drug rewards, such as opioids, endocannabinoids, dopamine and noradrenaline, have an important modulatory role in the performance of social play. Drugs of abuse from various pharmacological classes have facilitating effects on social play, under certain circumstances, most likely because they enhance the positive emotional properties of social play. The overlap in neural pathways involved in mediating rewarding social interactions and the positive subjective properties of drugs of abuse may explain the clinical relationship between social behavior and addictive behavior. The ability to make profitable short- and long-term decisions, select optimal behavioral strategies and inhibit prepotent responses can be considered as expressions of cognitive control. Impairments in these cognitive abilities can have tremendous influence on daily life and are associated with a variety of psychiatric disorders. Pharmacological manipulations targeting monoaminergic reuptake demonstrated that dopamine (DA), noradrenaline (NA) and serotonin (5-HT) interfere in different ways with the behavioral constructs underlying cognitive control. Elevation of DA neurotransmission increases impulsive action, whereas it reduces impulsive choice. Increasing NA or 5-HT neurotransmission reduces impulsive action, but has no effect on impulsive choice.Simultaneous blockade of DA and NA disrupts decision making, reflected by a relative decrease in choice for the advantageous choice options. In our research it is demonstrated that a disrupted social development by social isolation during early adolescence, i.e. postnatal day 21 until 42, when social play is highly abundant, affects cognitive development, prefrontal DA function and creates an increased vulnerability for drug addiction later in life. Early adolescent social isolation resulted in an increase of impulsive action and blunted response to DA reuptake inhibitors under demanding conditions in the 5-choice serial reaction time task. Moreover, instead of a normal development of preference for the advantageous options, socially isolated rats had a disrupted acquisition of a profitable choice strategy in the first session of the rat gambling task. The impaired cognitive control was accompanied by a loss of sensitivity to DA of pyramidal neurons in the adult medial PFC. Furthermore, adolescent social isolation resulted in an enhanced acquisition and increased motivation for low doses of cocaine during adulthood. These deficits were all observed during adulthood after several months of re-socialization, indicating the long-lasting impact of early social life events.