Adolescent peer-rejection persistently alters pain perception and CB1 receptor expression in female rats Peggy Schneider a,1 , Christin Hannusch a,1 , Christian Schmahl b , Martin Bohus b , Rainer Spanagel c , Miriam Schneider a,n a Research Group Developmental Neuropsychopharmacology, Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany b Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany c Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany Received 13 August 2012; received in revised form 28 March 2013; accepted 10 April 2013 KEYWORDS Social rejection; Adolescence; Social play behavior; Pain; CB1 receptor; FAAH Abstract Peer-interactions are particularly important during adolescence and teenagers display enhanced sensitivity toward rejection by peers. Social rejection has been shown to induce alterations in pain perception in humans. However, the neurobiological consequences of adolescent social rejection have yet to be extensively characterized, and no appropriate animal model is available. Here, we propose inadequate playful interactions in adolescent rats as a novel animal model for social peer-rejection and examine potential long-term consequences into adulthood. Acute social pairing of female adolescent Wistar rats with an age-matched rat from the less playful Fischer344 strain was found to alter social play and decrease pain reactivity, indicating Fischer rats as inadequate social partners for Wistar animals. Therefore, in a second experiment, adolescent female Wistar rats were either reared with another Wistar rat (adequate social rearing; control) or with a Fischer rat (inadequate social rearing; play- deprived). Beginning on day 50, all Wistar rats were group housed with same-strain partners and tested for behavioral, neurobiological and endocrine differences in adulthood. Playful peer-interactions were decreased during adolescence in play-deprived animals, without affecting social contact behavior. Consequently, adult play-deprived rats showed decreased pain sensitivity and increased startle reactivity compared to controls, but did not differ in activity, anxiety-related behavior or social interaction. Both groups also differed in their endocrine stress-response, and expression levels of the cannabinoid CB1 receptor were increased in the thalamus, whereas FAAH levels were decreased in the www.elsevier.com/locate/euroneuro 0924-977X/$ - see front matter & 2013 Elsevier B.V. and ECNP. All rights reserved. http://dx.doi.org/10.1016/j.euroneuro.2013.04.004 n Correspondence to: Research Group Developmental Neuropsychopharmacology, Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159 Mannheim, Germany. Tel.: +49 621 17036269; fax: +49 621 17036255. E-mail address: miriam.schneider@zi-mannheim.de (M. Schneider). 1 These authors contributed equally. European Neuropsychopharmacology (2014) 24, 290–301