Behavioural Brain Research 203 (2009) 43–47 Contents lists available at ScienceDirect Behavioural Brain Research journal homepage: www.elsevier.com/locate/bbr Research report Neural responses of rats in the forced swimming test: [F-18]FDG micro PET study Dong-Pyo Jang a , So-Hee Lee a , Sang-Yoon Lee a , Chan-Woong Park a , Zang-Hee Cho a , Young-Bo Kim a,b,∗ a Neuroscience Research Institute, Gachon University of Medicine and Science, 1198 Kuwol-dong, Namdong-gu, Incheon 405-760, Republic of Korea b Department of Neurosurgery, Gachon University of Medicine and Science, 1198 Kuwol-dong, Namdong-gu, Incheon 405-760, Republic of Korea article info Article history: Received 3 January 2009 Received in revised form 4 April 2009 Accepted 13 April 2009 Available online 24 April 2009 Keywords: Micro PET Forced swimming test [F-18]Fluorodeoxyglucose FDG Periaqueductal gray abstract The forced swimming test (FST) is a widely used tool in the assessment of behavioral despair and pre- diction of response to antidepressants. However, the neural mechanisms underlying behavioral changes between pretest and test sessions of the FST remain unclear. In this study, we investigated changes in rat brain activity during the FST using [F-18]Fluorodeoxyglucose micro PET. In both pretest and test sessions, the activity of the cerebellum and striatum increased, whereas significant deactivation was observed in the hippocampus, inferior colliculus, orbital cortex, and insula. The periaqueductal gray (PAG) region activated markedly in the pretest session, but did not activate in the test session. There was a signifi- cant increase in immobility and a decrease in climbing during the behavioral analysis test session. These results suggest that the PAG region may play an important role in the modulation of FST coping strategies subsequent to failure of the escape response during the pretest session. © 2009 Elsevier B.V. All rights reserved. 1. Introduction The forced swimming test (FST), first described by Porsolt et al. in 1977, is a tool widely used in the assessment of behavioral despair and prediction of response to antidepressants in animals, which is relatively simple to set up and has sensitivity to antidepressants [10,18,22]. In the FST, a rat is first exposed to a swimming stress, followed by a second exposure 24h later to a similar stress. When rats are forced to swim for the first time (the “pretest”), they react by moving vigorously to escape from the stressful situation. Then, their attempts to escape decline and they become immobile, lack- ing any active responses [27]. During the second exposure to forced swimming (the “test”), the immobility behavior is greatly increased compared with this response in the first exposure. Several inter- pretations have attempted to characterize behavioral changes that occur in the FST. Increased immobility has been proposed as “behav- ioral despair” or a state similar to “learned helplessness” [8,26]. Alternatively, the increased immobility observed in the test session of the FST could be a passive coping strategy to reduce expenditure of energy after failure of active and aggressive response during the pretest session [33,34]. Similarly, another proposal suggests that behavioral immobility shows an adaptive response to stressful sit- uations [4,14]. Familiarization with the experimental circumstance and a decrease in the sensation of emergency by exposure to a water ∗ Corresponding author at: Neuroscience Research Institute, Gachon University of Medicine and Science, 198 Kuwol-dong, Namdong-gu, Incheon 405-760, Republic of Korea. Tel.: +82 32 460 2083; fax: +82 32 460 8230. E-mail address: neurokim@gachon.ac.kr (Y.-B. Kim). cylinder (with or without water) during the pretest session also affect the immobility response [5]. While various interpretations of the behavioral changes during FST have been proposed, few studies have used functional neu- roimaging techniques to explore the neural mechanisms underlying these changes [12]. Recently, an in vivo neuroimaging technology that measures accumulation of [F-18]Fluorodeoxyglucose (FDG) during uptake time using micro PET has been developed, provid- ing an opportunity to observe brain activity in small animals [23]. In particular, this technique allows examination of whole brain function without the effects of anesthesia or animal sacrifice and enables studies that require serial brain imaging of the same sub- ject. In this study, we investigated functional changes of rat whole brain between pretest and test sessions of FST using [F-18]FDG micro PET neuroimaging. 2. Materials and methods 2.1. Animal handling Seventeen healthy adult male Sprague–Dawley rats (300–350 g; Orient, Pyeong- taek, Korea) were used in this study. All procedures were performed in accordance with the National Institutes of Health Guidelines for Animal Research (Guide for the Care and Use of Laboratory Animals). Animals were housed in pairs with a 12h light/dark cycle (lights on at 8:00), 50%–60% humidity, and free access to food and water ad libitum. The animals were acclimatized to the laboratory for four days before the beginning of the experiments. 2.2. Behavioral test and [F-18]FDG micro PET imaging The experimental design is shown in Fig. 1; micro PET scans were conducted in all rats three separate times: control, pretest, and test condition. To collect control data, we performed an [F-18]FDG scan on all animals one week before performing the FST 0166-4328/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2009.04.020