title: Inhibitory avoidance learning in zebrafish (Danio rerio): effects of shock intensity and unraveling differences in task performance.
abstract: The zebrafish (Danio rerio) is increasingly used as a model in neurobehavioral and neuroendocrine studies. The inhibitory avoidance paradigm has been proposed as tool to study mechanisms underlying learning and memory in zebrafish. In this paradigm subjects receive a shock after entering the black compartment of a black-white box. On the next day, latency to enter the black compartment is assessed; higher latencies are indicative of increased avoidance learning. Here, we aimed to understand the effects of different shock intensities (0, 1, 3, and 9 V) and to unravel variation in inhibitory avoidance learning in an in-house reared Tuebingen Long-Fin zebrafish (D. rerio) strain. While median latencies had increased in the 1, 3, and 9 V groups, no increase in median latency was found in the 0 V group. In addition, higher shock intensities resulted in a higher number of avoiders (latency ≥180 s) over nonavoiders (latency <60 s). Both changes are indicative of increased avoidance learning. We assessed whole-body cortisol content and the expression levels of genes relevant to stress, anxiety, fear, and learning 2 h after testing. Shock intensity was associated with whole-body cortisol content and the expression of glucocorticoid receptor alpha [nr3c1(alpha)], cocaine- and amphetamine-regulated transcript (cart4), and mineralocorticoid receptor (nr3c2), while avoidance behavior was associated with whole-body cortisol content only. The inhibitory avoidance paradigm in combination with measuring whole-body cortisol content and gene expression is suitable to unravel (genetic) mechanisms of fear avoidance learning. Our data further show differences in brain-behavior relationships underlying fear avoidance learning and memory in zebrafish. These findings serve as starting point for further unraveling differences in brain-behavior relationships underlying (fear avoidance) learning and memory in zebrafish.
authors.affiliation: 1 Department of Animal Physiology, Institute of Water and Wetland Research, Radboud University Nijmegen , Nijmegen, The Netherlands .
authors.forename: Remy
authors.initials: R
authors.lastname: Manuel
authors.forename: Marnix
authors.initials: M
authors.lastname: Gorissen
authors.forename: Carme Piza
authors.initials: CP
authors.lastname: Roca
authors.forename: Jan
authors.initials: J
authors.lastname: Zethof
authors.forename: Hans
authors.initials: H
authors.lastname: van de Vis
authors.forename: Gert
authors.initials: G
authors.lastname: Flik
authors.forename: Ruud
authors.initials: R
authors.lastname: van den Bos
mesh_terms: D000818:Animals; D001007:Anxiety; D001362:Avoidance Learning; D004597:Electroshock; D005239:Fear; D005260:Female; D005786:Gene Expression Regulation; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D008568:Memory; D011930:Reaction Time; D013312:Stress, Physiological; D015027:Zebrafish / Q000502:physiology*
chemical_list: D006854:Hydrocortisone