Effects of transgenic overproduction of CRH on anxiety‐like behaviour

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/arousal.