Behavioural Brain Research 203 (2009) 81–87 Contents lists available at ScienceDirect Behavioural Brain Research journal homepage: www.elsevier.com/locate/bbr Research report Anxiolytic effects of rapid amygdala kindling, and the influence of early life experience in rats Nigel C. Jones a,∗,1 , Gaurav Kumar a,1 , Terence J. O’Brien a,b,c , Margaret J. Morris d , Sandra M. Rees e , Michael R. Salzberg f a Department of Medicine, University of Melbourne, 4th Floor Clinical Sciences Building, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3052, Australia b Department of Neurology, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3052, Australia c Department of Surgery, University of Melbourne, 6th Floor Clinical Sciences Building, Royal Melbourne Hospital, Royal Parade, Parkville, Victoria 3052, Australia d Department of Pharmacology, University of New South Wales, School of Medical Sciences, Sydney, New South Wales 2052, Australia e Department of Anatomy and Cell Biology, University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia f Department of Psychiatry, University of Melbourne, St. Vincent’s Hospital, Victoria Parade, Fitzroy, Victoria 3065, Australia article info Article history: Received 24 December 2008 Received in revised form 15 April 2009 Accepted 19 April 2009 Available online 3 May 2009 Keywords: Epilepsy Anxiety Rapid kindling Maternal separation stress Psychiatric comorbidity abstract The incidence of psychiatric disturbances is elevated in temporal lobe epilepsy (TLE) patients. Early life stressful events are believed to have a major impact on mental health later in life, and increasing evidence suggests that such stresses may also promote a vulnerability to TLE. This study investigated whether subjecting rats to early life stress exacerbated mood and cognitive disturbances associated with the development of epilepsy. On postnatal days 2–14, rat pups were separated from their dams for either 180min/day (handling and maternal separation – HMS180, modelling early life stress) or 15min/day (control handling and maternal separation – HMS15). At 7 weeks, rats were implanted with a bipolar electrode into the left amygdala. Following recovery, one group of rats from each litter underwent rapid amygdala kindling (RAK) epileptogenesis, while another underwent sham kindling. One week following this, rats were subjected to behavioural tests assessing anxiety and cognition. HMS180-exposed rats kin- dled faster than HMS15 rats (p < 0.0001). RAK induced a potent anxiolytic effect as evidenced by increased % time spent in the open arms of the elevated plus maze, compared with sham kindled rats (p < 0.0001). This anxiolytic effect was also observed in the open field task, as evidenced by increased time spent in the inner area (p =0.010). Neither RAK nor maternal separation had any effect on cognitive function in the Morris water maze. We conclude that maternal separation stress accelerates limbic epileptogenesis in adult rats, and that RAK induces potent anxiolytic effects that are not influenced by such early life stressful events. © 2009 Elsevier B.V. All rights reserved. 1. Introduction A high proportion of patients with epilepsy exhibit psychiatric comorbidities, including depression, anxiety, psychoses, cognitive disorders and increased suicide ideation and attempts, which con- tribute greatly to impaired quality of life [17]. Although this is particularly associated with temporal lobe epilepsy (TLE), more recent studies have demonstrated that patients with other focal and generalised epilepsy syndromes are similarly affected [5,10,17]. The increased prevalence of these psychiatric disturbances has been variously attributed to the psychosocial consequences of living with epilepsy, the repeated damaging effects of seizures on the brain, ∗ Corresponding author. Tel.: +61 3 8344 3273; fax: +61 3 9347 1863. E-mail address: ncjones@unimelb.edu.au (N.C. Jones). 1 These authors contributed equally to this work. long-term medication effects, and even to a common underlying neurobiological abnormality [22,29]. Of note, many animal mod- els of TLE are reported to show a range of striking behavioural changes following development of the epilepsy, including inter- ictal alterations in anxiety states and depressive-like behaviours [3,23,25,26,38,39,48]. If the animal models of TLE utilized are accu- rate constructs of the clinical condition, these observations suggest that there is at least some neurobiological connection between the epilepsy and the psychiatric comorbidities observed in humans. Electrical kindling is a well-characterised animal model of TLE [14], whereby repeated electrical stimulation of various limbic brain structures, including the amygdala, results in a permanently height- ened excitable state. Conventional amygdala kindling, where two electrical stimulations are delivered per day, has been repeatedly used to investigate both the process of epileptogenesis [41], and also changes in interictal emotionality [26]. Rapid amygdala kin- dling (RAK), where up to 24 stimulations are given each day, is 0166-4328/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2009.04.023