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Journal Article

Effects of transgenic overproduction of CRH on anxiety-like behaviour

MPS-Authors

van Gaalen,  MM
Max Planck Institute of Psychiatry, Max Planck Society;

Stenzel-Poore,  MP
Max Planck Institute of Psychiatry, Max Planck Society;

Holsboer,  F
Max Planck Institute of Psychiatry, Max Planck Society;

Steckler,  T
Max Planck Institute of Psychiatry, Max Planck Society;

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Citation

van Gaalen, M., Stenzel-Poore, M., Holsboer, F., & Steckler, T. (2002). Effects of transgenic overproduction of CRH on anxiety-like behaviour. European Journal of Neuroscience, 15(12), 2007-2015.


Cite as: http://hdl.handle.net/11858/00-001M-0000-000E-A1D1-8
Abstract
Central administration of corticotropin-releasing hormone increases anxiety-like behaviour and arousal in rodents, and increased anxiety-like behaviour has been shown in mice overproducing corticotropin-releasing hormone on an elevated plus maze and in a dark-light emergence task. However, evidence is accumulating that measures obtained from different anxiety tasks may reflect different aspects of anxiety-like behaviour in animals. We therefore tested mice overproducing corticotropin-releasing hormone in a battery of paradigms, studying spontaneous behaviour after a mild stressor, tasks of innate anxiety-like behaviour (light-dark box), lick suppression (Vogel conflict), conditioned fear, and forced swimming. Exploratory behaviour was studied in a 16-hole board task. Furthermore, pain threshold, water intake, locomotor activity and sensorimotor learning/co-ordination were tested to control for confounding factors. In line with previous findings, increased anxiety-like behaviour of transgenic mice was observed in the light-dark box paradigm. However, no differences were seen in the conflict paradigm. Conditioned fear was decreased 1 h but not 24 h after conditioning in transgenic mice, and immobility was increased in forced swimming in corticotropin-releasing hormone overexpressors. Locomotor activity in a novel open field and on the hole board was reduced in transgenics. Exploratory behaviour (hole pokes) was reduced during initial exploration of an unfamiliar hole board. Moreover, sensorimotor performance on a rotorod was impaired, and water intake was reduced in corticotropin- releasing hormone overproducing mice, while no changes were seen in nociception. No differences in locomotor activity were seen in a second group of mice, tested in a familiar open field. When these animals were challenged with diazepam, transgenic mice were less susceptible to the sedative effects of the drug on locomotor activity. These data suggest that corticotropin-releasing hormone overproduction leads to specific effects in a subset of anxiety paradigms, and that these transgenic mice suffer from a motor deficit in addition to altered anxiety-like behaviour/arousa