INDIVIDUAL DIFFERENCES IN THE FORCED SWIMMING TEST AND THE EFFECT OF ENVIRONMENTAL ENRICHMENT: SEARCHING FOR AN INTERACTION A. SEQUEIRA-CORDERO, a,b * A. MORA-GALLEGOS, b P. CUENCA-BERGER a,b,c AND J. FORNAGUERA-TRI ´ AS b,c a Instituto de Investigaciones en Salud, Universidad de Costa Rica, ZIP code 11501-2060, San Pedro, San Jose ´, Costa Rica b Centro de Investigacio ´n en Neurociencias, Universidad de Costa Rica, ZIP code 11501-2060, San Pedro, San Jose ´, Costa Rica c Depto. De Bioquı´mica, Escuela de Medicina, Universidad de Costa Rica, ZIP code 11501-2060, San Pedro, San Jose ´, Costa Rica Abstract—Animals with low and high immobility in the forced swimming test (FST) differ in a number of neurobehavioral factors. A growing body of evidence suggests that the expo- sure to enriched environments mediates a number of changes in the brain. Therefore, we studied if animals’ indi- viduality can somehow modulate the response to environ- mental stimuli. Male rats were classified according to their immobility time scores in the FST test session as animals with low, medium or high immobility. Then, rats from groups with low and high immobility were randomly distributed in two groups to be reared in different housing conditions (i.e., enriched and standard conditions) during 8 weeks. Animals were subjected to the open field test (OFT) before and 6 weeks after the start of housing protocol. Rats with high immobility in the FST also showed high ambulation and high rearing time in the first OFT. Such findings were not observed in the second OFT. Conversely, an effect of environmental enrichment was found in the second OFT where enriched ani- mals showed lower ambulation and higher grooming time than the standard control group. Rats were sacrificed after the housing protocol and neurochemical content and/or gene expression were studied in three different brain regions: the prefrontal cortex, the hippocampus and the nucleus accum- bens. Rats with low immobility showed significantly higher accumbal 5-HT levels than animals with high immobility, whereas no neurochemical differences were observed between enriched and standard animals. Regarding expres- sion data, however, an effect of enrichment on accumbal cor- ticotropin-releasing factor (CRF) and its receptor 1 (CRFR1) levels was observed, and such effect depended on immobility levels. Thus, our results not only allowed us to identify a num- ber of differences between animals with low and high immo- bility or animals housed in standard and enriched conditions, but also suggested that animals’ individuality modulated in some way the response to environmental stim- uli. Ó 2014 IBRO. Published by Elsevier Ltd. All rights reserved. Key words: individual differences, environmental enrich- ment, neurotransmitters, gene expression, nucleus accum- bens. INTRODUCTION The study of behavioral individual differences, that is, classification of individuals according to systematic variations of specific behaviors, has shown to be a very useful tool in the research of brain function and mood disorders (Ho et al., 2002; Lathe, 2004; Kazlauckas et al., 2005; Go¨risch and Schwarting, 2006). In order to analyze individual behavior a cohort of animals is exposed to a behavioral test and, afterward, divided into at least two groups (i.e., high and low responders) according to the scores for specific behavioral responses (for a review see Pawlak et al., 2008). Given that an individual phenotype can be influenced by several interacting factors such as genetic variation, endocrine status and environmental effects (Lathe, 2004), the study of individual differences provides an important methodological approach to identify such factors and to analyze components underlying the development of mood disorders (Pawlak et al., 2008). Accordingly, several groups have used this approach to study anxiety- (Borta and Schwarting, 2005; Herrero et al., 2006; Antoniou et al., 2008) and depression- related behaviors (Taghzouti et al., 1999; Naudon and Jay, 2005; Enrı´quez-Castillo et al., 2008). On the other hand, the environment exerts a significant modulator effect on brain function and, therefore, it plays a relevant role in both normal and atypical development of the central nervous system (Heim et al., 2004; Paus, 2013). Environmental enrichment has shown to be a useful approach to comprehend functional issues underlying the effects of psychosocial and physical environments (Petrosini http://dx.doi.org/10.1016/j.neuroscience.2014.01.047 0306-4522/Ó 2014 IBRO. Published by Elsevier Ltd. All rights reserved. * Correspondence to: A. Sequeira-Cordero, Instituto de Investigaci- ones en Salud (INISA), Universidad de Costa Rica, ZIP code 11501-2060, San Pedro, Costa Rica. Tel: +506-2511-3482; fax: +506-2511-5130. E-mail address: bioaseq@gmail.com (A. Sequeira-Cordero). Abbreviations: 5-HIAA, 5-hydroxyindoleacetic acid; 5-HT, serotonin; BDNF, brain-derived neurotrophic factor; CRF, corticotropin-releasing factor; CRFR1, CRF receptor 1; DA, dopamine; DOPAC, 3,4- dihydroxyphenylacetic acid; EDTA, ethylenediaminetetraacetic acid; FST, forced swimming test; HPC, hippocampus; HPLC, high- performance liquid chromatography; HPRT1, hypoxanthine phosphoribosyltransferase 1; NAc, nucleus accumbens; NE, noreprinephrine; OFT, open field test; PFC, prefrontal cortex; PND, postnatal day; PPIA, peptidylprolil isomerase A; TrkB, tropomyosin receptor kinase B. Neuroscience 265 (2014) 95–107 95