Neurobiological Consequences and Mechanisms of Early Social Rejection Experiences in an Animal Model with relevance for Borderline Personality Disorder
Final Report Abstract
The aim of the application was to establish an animal model for early social rejection to investigate the impact of adolescent trauma on psychosocial illnesses across the lifespan. In a second step, we examined the neuronal mechanisms of early social rejection. Social rejection induces stress in hu-mans and plays a significant role in borderline personality disorder (BPS). We succeeded in establish-ing a new animal model for the long-term consequences of earlier aversive social experiences. Due to the deprivation of specific social needs during the childhood and / or adolescence phase, ongoing impairments in the behavior of adult female rats (comparable to certain core symptoms of BPS) were found. In male rats, early social rejection tends to play a more protective role, and such animals tend to be less susceptible to addiction. In comparative studies with another animal model, early social isolation, female animals showed no long-lasting changes, especially in the social and emotional do-mains. Early social rejection leads to strong and persistent changes in the endocannabinoid system. Thus, persistent adverse effects on social behavior and pain perception are associated with specific up-regulation of the cannabinoid receptor 1 (CB1R) in the amygdala and thalamus. Consequently, behavioral changes in adult rats can be restored by a low-dose dose of rimonabant. Long-lasting neurobiological adaptations within the oxytocin system (especially an up-regulation of the oxytocin receptor (OCYR in the paraventricular thalamic nucleus) after social peer-rejection were also found. Since CB1R and OXYR appear to be important for mediating long-term consequences of social peer-rejection, we suggest that manipulation of CB1R and OXYR activity in BPS may be useful.
Publications
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(2015). Enhanced functional activity of the cannabinoid type-1 receptor mediates adolescent behavior. The Journal of Neuroscience, 35(41), 13975-88
Schneider, M., Kasanetz, F., Lynch, D. L., Friemel, C. M., Lassalle, O., Hurst, D. P., . . . Spanagel, R.
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(2016). Adolescent social rejection alters pain processing in a CB1 receptor dependent manner. European Neuropsychopharmacology, 26(7), 1201-1212
Schneider, P., Pätz, M., Spanagel, R., & Schneider, M.
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(2016). Adverse social experiences in adolescent rats result in enduring effects on social competence, pain sensitivity and endocannabinoid signaling. Frontiers in Behavioral Neuroscience, 10(203)
Schneider, P., Bindila, L., Schmahl, C., Bohus, M., Meyer-Lindenberg, A., Lutz, B., . . . Schneider, M.
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(2017). The cannabinoid receptor 1 as a key mediator of adolescent behavior. Neuropsychopharmacology, 42(1), 367
Spanagel, R., & Kiefer, F.
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(2018). Alterations of the biological clock may contribute to the emergence of mental disorders during adolescence. Biological Psychiatry, 83(12), 978-980
Spanagel, R.
