title: Unpredictable chronic stress decreases inhibitory avoidance learning in Tuebingen long-fin zebrafish: stronger effects in the resting phase than in the active phase.
abstract: Zebrafish (Danio rerio Hamilton) are increasingly used as a model to study the effects of chronic stress on brain and behaviour. In rodents, unpredictable chronic stress (UCS) has a stronger effect on physiology and behaviour during the active phase than during the resting phase. Here, we applied UCS during the daytime (active phase) for 7 and 14 days or during the night-time (resting phase) for 7 nights in an in-house-reared Tuebingen long-fin (TLF) zebrafish strain. Following UCS, inhibitory avoidance learning was assessed using a 3 day protocol where fish learn to avoid swimming from a white to a black compartment where they will receive a 3 V shock. Latencies of entering the black compartment were recorded before training (day 1; first shock) and after training on day 2 (second shock) and day 3 (no shock, tissue sampling). Fish whole-body cortisol content and expression levels of genes related to stress, fear and anxiety in the telencephalon were quantified. Following 14 days of UCS during the day, inhibitory avoidance learning decreased (lower latencies on days 2 and 3); minor effects were found following 7 days of UCS. Following 7 nights of UCS, inhibitory avoidance learning decreased (lower latency on day 3). Whole-body cortisol levels showed a steady increase compared with controls (100%) from 7 days of UCS (139%), to 14 days of UCS (174%) to 7 nights of UCS (231%), suggestive of an increasing stress load. Only in the 7 nights of UCS group did expression levels of corticoid receptor genes (mr, grα, grβ) and of bdnf increase. These changes are discussed as adaptive mechanisms to maintain neuronal integrity and prevent overload, and as being indicative of a state of high stress load. Overall, our data suggest that stressors during the resting phase have a stronger impact than during the active phase. Our data warrant further studies on the effect of UCS on stress axis-related genes, especially grβ; in mammals this receptor has been implicated in glucocorticoid resistance and depression.
authors.affiliation: Department of Organismal Animal Physiology, Institute for Water and Wetland Research, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands r.manuel@science.ru.nl.
authors.forename: Remy
authors.initials: R
authors.lastname: Manuel
authors.affiliation: Department of Organismal Animal Physiology, Institute for Water and Wetland Research, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
authors.forename: Marnix
authors.initials: M
authors.lastname: Gorissen
authors.affiliation: Department of Organismal Animal Physiology, Institute for Water and Wetland Research, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Zethof
authors.affiliation: Uni Research AS, Thormøhlensgt. 49B, N-5006 Bergen, Norway.
authors.forename: Lars O E
authors.initials: LO
authors.lastname: Ebbesson
authors.affiliation: IMARES, Wageningen UR, P. Box 77, 4401 NT Yerseke, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: van de Vis
authors.affiliation: Department of Organismal Animal Physiology, Institute for Water and Wetland Research, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Flik
authors.affiliation: Department of Organismal Animal Physiology, Institute for Water and Wetland Research, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
authors.forename: Ruud
authors.initials: R
authors.lastname: van den Bos
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology; D004558:Electric Stimulation; D020869:Gene Expression Profiling; D006854:Hydrocortisone / Q000378:metabolism; D023421:Models, Animal; D011930:Reaction Time / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013312:Stress, Physiological / Q000502:physiology*; D013997:Time Factors; D015027:Zebrafish / Q000502:physiology*
chemical_list: D011965:Receptors, Glucocorticoid; D006854:Hydrocortisone
keywords: Behaviour; Danio rerio; Diurnal effects; Gene expression; Telencephalon