Developmental Psychobiology Debra A. Lynn Gillian R. Brown School of Psychology University of St Andrews South Street, St Andrews Fife KY16 9JP, UK E-mail: dal5@st-andrews.ac.uk The Ontogeny of Anxiety-Like Behavior in Rats from Adolescence to Adulthood ABSTRACT: In human beings, susceptibility to anxiety disorders can be relatively high during adolescence. Understanding the ontogeny of anxiety-like behavior in laboratory rodents has implications for developing anxiolytic drugs that are suitable for this age group. Given the dearth of information about adolescent rodents, this study examined the response of both male and female adolescent, late adolescent, young adult, and older adult rats to three tests of anxiety-like behavior: the emergence test (ET), open ﬁeld (OF), and elevated plus-maze (EPM). The results showed that adolescent rats exhibited a higher anxiety-like response than adults on each test; the amount of locomotion in the OF and percentage of time spent on the open arms of the EPM increased across the age groups, while older adult rats made the fewest start box re-entries in the ET. These results support the hypothesis that adolescent rats have a more pronounced response to stressors than do adults. 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 731–739, 2010. Keywords: adolescence; anxiety; rats; open ﬁeld; elevated plus-maze; sex differences INTRODUCTION Adolescence is a period of heightened susceptibility to anxiety disorders for some individuals (Crick & Zahn- Waxler, 2003; Paus, Keshavan, & Giedd, 2008; Petersen, 1988), potentially due to the developmental changes in gonadal and adrenal hormone production that accompany this stage of life (Hayward & Sanborn, 2002; McCormick & Mathews, 2007; Reardon, Leen-Feldner, & Hayward, 2009; Spear, 2000a,b). The development of new anxio- lytic drugs for adolescents is important given that currently available anxiolytic drug treatments can have signiﬁcant negative side effects in this age group (Hammad, Laughren, & Racoosin, 2006; Malkesman et al., 2009). While research on anxiety-like behavior in laboratory animals has important implications for the Received 7 January 2010; Accepted 5 April 2010 Correspondence to: D. A. Lynn Contract grant sponsor: Wellcome Trust Contract grant sponsor: School of Psychology, University of St Andrews Published online 12 May 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/dev.20468 2010 Wiley Periodicals, Inc. development of new drugs, relatively little is known about the development of anxiety-like behavior in rodents. The aim of this study was, therefore, to investigate the ontogeny of anxiety-like behavior in rats from adolescence to adulthood. Anxiety-like behavior in rodents has commonly been assessed by recording how animals respond to a novel, potentially threatening environment (Litvin, Pentkowski, Pobbe, Blanchard, & Blanchard, 2008). In this study, we measured the response of rats to three novel pieces of apparatus: the emergence test (ET), the open ﬁeld (OF) and the elevated plus-maze (EPM). All of these tests assume that rats ﬁnd novel, exposed environments relatively aversive due to potential predation risk. The ET consists of a box or canopy that is placed into a novel arena (Grewel, Shepherd, Bill, Fletcher, & Dourish, 1997), and a fast emergence from the canopy is described as a low anxiety-like response (Ray & Hansen, 2004). The OF consists of a novel, enclosed space into which the animal is placed for a ﬁxed amount of time (Hall, 1934, 1936), and high levels of locomotion in the center of the OF is described as a low anxiety-like response (Prut & Belzung, 2003). The EPM consists of two open and two enclosed arms arranged in a plus-shape and raised above the ground (Handley & Mithani, 1984; Montgomery,