Effects of transgenic overproduction of CRH on anxiety-like behaviour

Eur J Neurosci. 2002 Jun;15(12):2007-15. doi: 10.1046/j.1460-9568.2002.02040.x.

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 decreased [corrected] 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.

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology
  • Anxiety / drug therapy
  • Anxiety / genetics
  • Anxiety / metabolism*
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Brain / drug effects
  • Brain / metabolism*
  • Brain / physiopathology
  • Brain Chemistry / drug effects
  • Brain Chemistry / genetics*
  • Corticotropin-Releasing Hormone / genetics
  • Corticotropin-Releasing Hormone / metabolism*
  • Dark Adaptation / drug effects
  • Dark Adaptation / physiology
  • Diazepam / pharmacology
  • Drinking / drug effects
  • Drinking / genetics
  • Exploratory Behavior / drug effects
  • Exploratory Behavior / physiology
  • Fear / drug effects
  • Fear / physiology
  • Genetic Predisposition to Disease
  • Male
  • Mice
  • Mice, Transgenic
  • Motor Activity / drug effects
  • Motor Activity / genetics
  • Neurons / drug effects
  • Neurons / metabolism*
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Photic Stimulation
  • Reaction Time / drug effects
  • Reaction Time / genetics
  • Stress, Physiological / genetics
  • Stress, Physiological / metabolism
  • Stress, Physiological / physiopathology
  • Up-Regulation / physiology*

Substances

  • Anti-Anxiety Agents
  • Corticotropin-Releasing Hormone
  • Diazepam