title: CREB deficient mice show inhibition and low activity in novel environments without changes in stress reactivity.
abstract: The ability to respond to unexpected or novel stimuli is critical for survival. Determining that a stimulus is indeed novel requires memory to ascertain its lack of familiarity. As the long-term synaptic changes involved in memory formation require the cAMP response element binding protein (CREB), we examined the extent to which CREB is involved in responses to novel environments. These environments typically trigger an endocrine stress response. Thus, we measured behavioural and stress hormone responses to three novel and one familiar environment in mice with a targeted disruption of the alpha and delta isoforms of the CREB gene (CREB(alphadelta-) deficient mice). We found CREB(alphadelta-) deficient mice to be less active and more inhibited in the elevated plus maze, open field, and light/dark box, without showing differences in anxiety-like behaviour. This inhibition is unique to novel environments because these mice display a normal phenotype in the home cage, a familiar environment. Although CREB(alphadelta-) deficient mice exhibit altered behaviour in novel environments, they show normal reactivity to mild and moderate stress as both basal and stress levels of corticosterone are similar to those of wild-type controls. This is the first report of CREB(alphadelta-) deficient mice to: (i) show altered behaviour, not related to learning and memory-associated behaviours, upon initial exposure to environments and (ii) serve as an animal model that can dissociate locomotor activity from anxiety-like behaviour in novel environments.
authors.affiliation: Mental Health Research Institute, University of Michigan, 205 Zina Pitcher Place, Ann Arbor, Michigan 48109, USA. hebda@umich.edu
authors.forename: Elaine K
authors.initials: EK
authors.lastname: Hebda-Bauer
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Watson
authors.forename: Huda
authors.initials: H
authors.lastname: Akil
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000502:physiology*; D004777:Environment; D005106:Exploratory Behavior / Q000502:physiology; D005838:Genotype; D007266:Inhibition, Psychological; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000502:physiology*; D009043:Motor Activity / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D011930:Reaction Time / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012727:Sex Characteristics; D013312:Stress, Physiological / Q000523:psychology*; D013997:Time Factors
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger