On the pleasurable, motivational and cognitive aspects of social play behavior: pharmacological studies in rats

Abstract

In comparison to naturally rewarding behaviors such as feeding and sex, relatively little is known about the neurobiological underpinnings of the positive emotional properties of social behavior. In the period between weaning and sexual maturity (i.e. childhood and adolescence in humans, roughly equivalent to the juvenile and adolescent stages in rodents) substantial changes occur in brain and behavior that are important for behavioral development. In particular, the social repertoire becomes increasingly complex and social interest shifts from the mother towards peers, mostly in the form of social play behavior. Social play behavior serves to facilitate social, physical, emotional and cognitive development. Understanding how social play behavior is generated and which brain areas and neurotransmitter systems modulate this behavior increases our knowledge about normal social behavior. Furthermore, several neuropsychiatric disorders such as attention-deficit/hyperactivity disorder (ADHD), disruptive behavior disorders (DBDs) and autism are characterized by impairments in social (play) behaviors. In addition, drugs of abuse, such alcohol and cocaine are often used in a social setting and this can influence social (play) behavior to a great extent. Furthermore, social disorders such as DBDs and ADHD are an important risk factor for alcohol and drug addiction. Therefore, understanding how drugs of abuse affect social (play) behavior is an important issue. Using operant and place conditioning as well as behavioral analysis of social play behavior in young rats, we aimed to elucidate the neurotransmitter systems and neural substrates underlying the pleasurable, motivational and cognitive aspects of social play behavior. We found that the psychostimulant amphetamine, like methylphenidate, exerts its play suppressant effects via α2-adrenoceptors. In contrast, the psychostimulant cocaine reduces social play by simultaneous increases in dopamine, noradrenaline and serotonin neurotransmission. We subsequently found that prefrontal (anterior cingulate and infralimbic cortex) and limbic subcortical (amygdala and habenula) regions are implicated in the effects of methylphenidate on social play, through noradrenergic neurotransmission. Using place conditioning and operant set-ups, we further elucidate the role of monoamines, opioids and cannabinoids in several aspects of social play behavior. With regard to monoamines, noradrenaline seems to modulate the motivation for social play behavior as well as its expression. For dopamine, clear but opposite roles were found on motivational and pleasurable aspects of social play. We found that the endogenous opioid system is involved in pleasurable and motivational aspects of social play, whereas endocannabinoid neurotransmission does not play a primary role in the motivational and pleasurable aspects of social play behavior. By analyzing the dynamics of social reward-related memories in place conditioning experiments, we found that this type of memories undergoes reconsolidation that depends on β-noradrenergic as well as glucocorticoid receptors, whereas mineralocorticoid, NMDA glutamatergic and CB1 cannabinoid receptors do not seem to be involved. Collectively, the studies in this thesis advance our understanding of the neural mechanisms involved in several aspects of social play behavior in rats. These studies provide important information on the neurobiology of normal, adaptive social behavior and may also give directions for the development of pharmacotherapies for social dysfunctions in psychiatric diseases.