Effects of central neuropeptides on social preference and social recognition in male rats

In chapters 2, 3, and 5 of this thesis, I aimed to add to the characterization of the involvement of central neuropeptides such as OT, AVP, and NPS in basic social abilities, i.e. individual social recognition and social approach behavior. Both aspects of social behavior are essentially needed for proper performance of more complex social behaviors, like aggression, sexual behavior or pair bonding. Additionally, in chapters 2, 3, and 4, I investigated the effects of different social stress paradigms, i.e. social defeat and MS, on social preference and social recognition abilities of male rats. In chapter 2, social stress was induced by an acute social defeat by a male con-specific. In contrast, in chapters 3 and 4, social stress was performed chronically during development, using MS, a deprivation of the pups from the dam during the first two weeks of life. The main prerequisite of all social interactions in rodents, including social recognition, is the ability to get in close contact with a con-specific. Therefore, in chapter 2, I adapted a social preference paradigm from mouse research (Berton et al., 2006) for rats to characterize social interaction/approach independent of innate anxiety. Using this new paradigm, I demonstrated that vehicle-treated male rats and mice have a natural preference for a social stimulus over a non-social stimulus, whereas blockade of endogenous OT resulted in social avoidance in male rats and even a total loss of social preference in male mice. Furthermore, I demonstrated specificity of this OT-mediated effect on social anxiety as both, rats injected with the anxiogenic PTZ and rats infused icv with a specific V1aR-A did not show changes in social preference behavior. Notably, icv infusion of OTR-A in different subnuclei of the amygdala did not result in alterations of social preference behavior. I further confirmed that acute social defeat induced social avoidance in male rats, when tested in the social preference paradigm 2 h later. However, social avoidance was only achieved, when the actual defeater rat was used as social stimulus during the social preference testing. Accordingly, acute icv OT administration prior to behavioral testing restored social preference in these rats - an effect that is also not mediated by the medial or central amygdala. In Chapter 3, I exposed male Wistar rats to postnatal stress, i.e. MS, and tested social memory, in the social discrimination paradigm, at juvenile (5 weeks) and adult age (16 weeks). Juvenile MS as well as juvenile and adult control rats recognized a juvenile con-specific after 30 and 60 min. In contrast, adult MS rats were able to recognize a juvenile con-specific only after an IEI of 30 min. Thereby, I was able to demonstrate impaired social memory abilities in postnatally-stressed adult male Wistar rats. Additionally, I measured septal AVP release via intracerebral microdialysis during social discrimination in male juvenile and adult, control and MS rats. While I observed a rise of extracellular septal AVP during acquisition of social memory, both in juvenile control and MS rats as well as in adult control rats, I found a blunted septal AVP release in adult MS rats. Interestingly, forced swimming-induced septal AVP release was not reduced in adult MS rats compared to controls. In order to counteract this blunted AVP release during social memory acquisition, I infused male MS rats with synthetic AVP using intraseptal retrodialysis. Indeed, synthetic AVP given during social memory acquisition was able to rescue social recognition abilities of formerly impaired adult MS rats. This indicates a causal connection between the impaired social recognition abilities in adult male MS rats and the blunted AVP release found in these rats. In chapter 4, we observed brain region-specific developmental changes in V1aR binding from juvenile rats over adolescence into adulthood using receptor autoradiography. The most pronounced age effect, in the form of increased V1aR binding, was found in the lateral septum. Exposure to MS significantly interfered with these developmental adaptations resulting in brain region- and age-dependent alterations in V1aRs. Most notably, MS increased V1aR binding in the piriform cortex (in adolescents and adults) and the lateral septum (in juveniles). In chapter 5, I was able to demonstrate that neither icv administration of synthetic NPS nor blockade of central NPS receptors was efficient to influence social preference and social recognition in male rats, despite its potent icv effects on non-social memory and anxiety. Moreover, I was able to show for the first time that synthetic NPS, applied nasally to male rats before performing in the object recognition paradigm and on the elevated plus-maze, was able to mimic the memory enhancing and anxiolytic effects of NPS that were already observed after icv administration.