title: The endocannabinoid system and associative learning and memory in zebrafish.
abstract: In zebrafish the medial pallium of the dorsal telencephalon represents an amygdala homolog structure, which is crucially involved in emotional associative learning and memory. Similar to the mammalian amygdala, the medial pallium contains a high density of endocannabinoid receptor CB1. To elucidate the role of the zebrafish endocannabinoid system in associative learning, we tested the influence of acute and chronic administration of receptor agonists (THC, WIN55,212-2) and antagonists (Rimonabant, AM-281) on two different learning paradigms. In an appetitively motivated two-alternative choice paradigm, animals learned to associate a certain color with a food reward. In a second set-up, a fish shuttle-box, animals associated the onset of a light stimulus with the occurrence of a subsequent electric shock (avoidance conditioning). Once fish successfully had learned to solve these behavioral tasks, acute receptor activation or inactivation had no effect on memory retrieval, suggesting that established associative memories were stable and not alterable by the endocannabinoid system. In both learning tasks, chronic treatment with receptor antagonists improved acquisition learning, and additionally facilitated reversal learning during color discrimination. In contrast, chronic CB1 activation prevented aversively motivated acquisition learning, while different effects were found on appetitively motivated acquisition learning. While THC significantly improved behavioral performance, WIN55,212-2 significantly impaired color association. Our findings suggest that the zebrafish endocannabinoid system can modulate associative learning and memory. Stimulation of the CB1 receptor might play a more specific role in acquisition and storage of aversive learning and memory, while CB1 blocking induces general enhancement of cognitive functions.
authors.affiliation: University of Bonn, Institute of Zoology - Department for Neuroethology and Sensory Ecology, Endenicher Allee 11-13, 53115 Bonn, Germany. Electronic address: truhl@uni-bonn.de.
authors.forename: Tim
authors.initials: T
authors.lastname: Ruhl
authors.affiliation: University of Bonn, Institute of Zoology - Department for Neuroethology and Sensory Ecology, Endenicher Allee 11-13, 53115 Bonn, Germany.
authors.forename: Kirstin
authors.initials: K
authors.lastname: Moesbauer
authors.affiliation: University of Bonn, Institute of Zoology - Department for Neuroethology and Sensory Ecology, Endenicher Allee 11-13, 53115 Bonn, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Oellers
authors.affiliation: University of Bonn, Institute of Zoology - Department for Neuroethology and Sensory Ecology, Endenicher Allee 11-13, 53115 Bonn, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: von der Emde
mesh_terms: D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology*; D005260:Female; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013687:Telencephalon / Q000187:drug effects / Q000378:metabolism*; D015027:Zebrafish / Q000378:metabolism*
chemical_list: D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D043884:Receptor, Cannabinoid, CB1
keywords: Associative learning; Avoidance; Endocannabinoid System; Fish; Memory; Motivation; Telencephalon