Short-term individual housing induced social deficits in female Mongolian gerbils: Attenuation by chronic but not acute imipramine A.R. Pickles c, * , J.J. Hagan a , D.N.C. Jones a , C.A. Hendrie b a GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park (North), Harlow CM19 5AW, UK b Institute of Psychological Studies, University of Leeds, Leeds LS2 9JT, UK c Institute of Membranes and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK article info Article history: Received 1 August 2011 Received in revised form 1 November 2011 Accepted 14 December 2011 Keywords: Depression Gerbils Animal models Imipramine abstract Mongolian gerbils are highly sensitive to manipulations of their social environments. Housing females individually for short periods (in the order of 7e21 days) has been shown to produce robust and reliable impairments of their subsequent social behaviour. These effects are typified by a marked reduction in the social investigation of an unfamiliar male in a neutral arena and/or a marked increases in levels of freezing whilst and only whilst they are being socially investigated (Immobile in contact). These responses demonstrate housing induced impaired motivation to socially interact. These effects have also been shown to be sensitive to treatment with chronic (but not acute) administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine. It was therefore of interest to know if similar effects would be produced by treatment with the tricyclic antidepressant Imipramine. This mixed NA/5-HT reuptake inhibitor first developed in the 1950’s is a commonly used standard in animal models of depression and remains in clinical use today. Female gerbils were individually housed for 7 days or maintained in single-sex groups of 4 for the same period. All animals were then randomly allocated to be administered with either 0, 10 or 20 mg/kg imipramine. Acute administration did not reverse the social impairments produced by the individual housing but did produce non-specific stimulant effects on locomotion in both housing conditions. These social impairments were however reduced after a further 14 days chronic treatment with 10 or 20 mg/kg imipramine and stimulant effects were no longer seen. Following chronic administration in group- housed animals locomotor stimulation was replaced with sedation, which resulted in a reduction in social behaviour. That is, opposite to the effect seen in Individual housed animals. It is therefore concluded that chronic treatment with imipramine serves to increase social behaviour but only in those animals with a pre-existing social deficit. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction Mongolian gerbils (Meriones unguiculatus) are small rodents native to eastern Mongolian and western Manchuria. In the wild they create complex burrow systems (Scheibler et al., 2006) and live in extended family groups (Bannikov, 1954). Reproduction is restricted to a dominant male and female pair and both help defend the territory, gather and store food and play an active role in parenting (Ågren, 1984a, 1984b; Ågren et al., 1989; Elwood and Broom, 1978). In the laboratory, separation of established male/female pairs has been shown to have profound effects on subsequent social behaviour which lasts for a period of several weeks (Hendrie and Starkey, 1998). This takes the form of females frequently display- ing a freeze response whilst and only whilst being socially inves- tigated (“immobile in contact”) and males typically showing reduced levels of aggression directed towards other males and in their social investigation of both sexes. These profiles are indicative of a reduced motivation to socially interact (e.g. Hendrie et al., 2003). Whilst it was initially thought that these behavioural effects were produced by the breaking of psychological bonds further studies showed that this wasn’t the whole explanation. Males were apparently bonded to a specific female, as the syndrome persisted even when they were housed with a different female. However, females showed these social deficits whenever and only whenever they were individually housed, regardless of the number or sex of the animals they were housed with before- hand (Starkey and Hendrie, 1998a, 1998b). Hence, individual * Corresponding author. E-mail address: a.r.pickles@leeds.ac.uk (A.R. Pickles). Contents lists available at SciVerse ScienceDirect Neuropharmacology journal homepage: www.elsevier.com/locate/neuropharm 0028-3908/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.neuropharm.2011.12.016 Neuropharmacology 62 (2012) 1993e1998