Behavioural Brain Research 218 (2011) 357–362 Contents lists available at ScienceDirect Behavioural Brain Research journal homepage: www.elsevier.com/locate/bbr Short communication Influence of transgenic corticotropin-releasing factor (CRF) over-expression on social recognition memory in mice Maki Kasahara a,1 , Lucianne Groenink b,c , Martien J.H. Kas b , Elisabeth Y. Bijlsma b,c , Berend Olivier b,c,d , Zoltán Sarnyai a,∗ a Department of Pharmacology, University of Cambridge, Cambridge, UK b Department of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, University of Utrecht, Utrecht, The Netherlands c Rudolf Magnus Institute of Neuroscience, University of Utrecht, Utrecht, The Netherlands d Department of Psychiatry, Yale University, New Haven, CT, USA article info Article history: Received 14 November 2010 Received in revised form 14 December 2010 Accepted 20 December 2010 Available online 28 December 2010 Keywords: Corticotropin-releasing factor Stress Transgenic mice Habituation Social recognition Social discrimination Memory abstract We examined juvenile social recognition and discrimination in mice with early post-natal onset, trans- genic CRF over-expression (CRF-OE) and in their wild-type littermates (WT). CRF-OE mice showed enhanced social investigation during the first encounter, normal short-term and facilitated long-term social recognition memory, compared to WT. These results suggest that chronically elevated brain CRF tone may contribute in better remembering ethologically relevant and emotionally salient stimuli, such as social interaction. © 2010 Elsevier B.V. All rights reserved. Social recognition, the ability to distinguish familiar from novel conspecifics, is critical for display of appropriate social behaviours, therefore for survival in a socially-structured environment [9]. Rodents are highly social animals and form a ‘social memory’, when the memory of a recently encountered individual is retained for some period of time [9]. This is essential for the animal to show the appropriate behaviours upon encountering the same individ- ual in the future. Social recognition memory can be inferred by a decrease in the frequency of social investigation after repeated exposure to a conspecific, often termed ‘habituation’ [38], which has been thought to reflect the formation of memory for the specific individual. Therefore, the need to further investigate the familiar conspecific is reduced. This form of learning can be modulated by a variety of neuropeptides, oxytocin and vasopressin, in particu- lar, across different mammalian species, including humans [29,32]. ∗ Corresponding author at: Department of Pharmacology, University of Cam- bridge, Tennis Court Road, Cambridge, CB2 1PD, UK, Tel.: +44 1223 330269, fax: +44 1223 334 040. E-mail address: zs220@cam.ac.uk (Z. Sarnyai). 1 Present address: Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden. Interestingly, both of these pro-social neuropeptides are highly responsive to changes in the environment and are considered as stress hormones [7]. However, there is relatively little informa- tion available on the possible effects of the main stress mediator neuropeptide, corticotropin-releasing factor (CRF), on social recog- nition memory. CRF is a 41-amino acid peptide released from neurons in the brain that contribute to the behavioural, hormonal and autonomic response to stress [16]. Acute, central administration of CRF mim- ics effects of stress and CRF receptor antagonists can prevent stress-induced behavioural responses [16]. Persistent increase in the activity of the brain CRF systems has been implicated in a num- ber of stress-related psychopathology, such as affective disorders [17] and drug addiction [34] and in cognitive decline [14]. It has been shown that acute administration of CRF exerts an inhibitory effect on social interactions in rats [5,6,27]. On the other hand, social recognition memory can be positively modulated by increas- ing endogenous CRF tone, as demonstrated by the effects of acute administration of a CRF receptor antagonist and a CRF binding pro- tein inhibitor in rats [15]. Therefore, it is of interest to investigate the effects of chronic, central CRF hyperactivity on social recogni- tion memory. To this end, we have developed a CRF transgenic line using a chimeric CRF transgene comprising the murine Thy-1.2 pro- 0166-4328/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2010.12.029