Effects of transgenic overproduction of CRH on anxiety-like behaviour.
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.
van Gaalen
Marcel M
MM
Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, D-80804 Munich, Germany. mm.van_gaalen.pharm@med.vu.nl
Stenzel-Poore
Mary P
MP
Holsboer
Florian
F
Steckler
Thomas
T
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics*; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D003623:Dark Adaptation / Q000187:drug effects / Q000502:physiology; D003975:Diazepam / Q000494:pharmacology; D004326:Drinking / Q000187:drug effects / Q000235:genetics; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005239:Fear / Q000187:drug effects / Q000502:physiology; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010775:Photic Stimulation; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D015854:Up-Regulation / Q000502:physiology*
D014151:Anti-Anxiety Agents; D003346:Corticotropin-Releasing Hormone; D003975:Diazepam