Neurobiological Consequences and Mechanisms of Early Social Rejection Experiences in an Animal Model with relevance for Borderline Personality Disorder

• Applicant: Professor Dr. Rainer Spanagel, since 6/2018
• Subject Area: Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 190034061

The major aim of the present proposal is to further elucidate the molecular consequences and mechanisms of social rejection in a rodent model with relevance to BPD. Social rejection is a major source of distress and has been implicated in the development of various psychiatric disorders including BPD. During the first funding period, we established a novel animal model for persistent consequences of early adverse social experiences in laboratory rats (Associated Project 1). By depriving animals of specific social requirements during childhood and adolescence we were able to evoke persistent behavioral changes in adult female rats that resemble core aspects of BPD (e.g. disturbed social interaction and recognition, and decreased pain sensitivity), as well as alterations in the endocannabinoid system (ECS), such as regionally enhanced levels of the endocannabinoid anandamide (AEA). The neurobiological consequences and mechanisms linked to social rejection are still largely unknown. Here, we aim to further examine these processes by investigating the consequences of deprivation of social requirements in adolescent rats ¿ alone, and in combination with early variances in the quality of mother-infant interaction. Our investigations will focus on neurochemical systems involved in the modulation of social behavior and pain processing: the ECS, the central oxytocin and the endogenous opioid system. Here, we plan to utilize imaging techniques (positron emission tomography) to enable a future translational approach with human studies. Additionally, we will apply molecular and neurochemical techniques and assess behavioral changes. Based on our previous findings, we now also intend to monitor the time course of neurobiological consequences of social rejection experiences throughout adolescence more closely, in order to shed light on the time course of the mechanistic processes mediating the persistent behavioral and neurobiological changes in adulthood. Furthermore, in order to gain a causal link between a given molecular change and a specific BPD-like behavioral feature we will use a regional viral-mediated gene transfer approach in an additional rescue experiment. A first target will be the normalization of enhanced amygdalar AEA levels and the hereby expected normalization of pain perception and social impairments. Other identified persistent molecular changes will be also selectively targeted by viral-mediated gene transfer. This approach will not only provide a mechanistical insight for BPD but will also deliver new intervention strategies for our CRU.

• DFG Programme: Clinical Research Units
• Subproject of: KFO 256: Mechanisms of Disturbed Emotion Processing in Borderline Personality Disorder
• Ehemalige Antragstellerin: Privatdozentin Dr. Miriam Schneider, until 5/2018