Acute administration of THC impairs spatial but not associative memory function in zebrafish

Abstract

Rationale: The present study examined the effect of acute administration of endocannabinoid receptor CB1 ligand δ-9-tetrahydrocannabinol (THC) on intracellular signalling in the brain and retrieval from two different memory systems in the zebrafish (Danio rerio). Methods: First, fish were treated with THC and changes in the phosphorylation level of mitogen-activated protein (MAP) kinases Akt and Erk in the brain were determined 1 h after drug treatment. Next, animals of a second group learned in a two-alternative choice paradigm to discriminate between two colours, whereas a third group solved a spatial cognition task in an open-field maze by use of an ego-allocentric strategy. After memory acquisition and consolidation, animals were pharmacologically treated using the treatment regime as in the first group and then tested again for memory retrieval. Results: We found an enhanced Erk but not Akt phosphorylation suggesting that THC treatment specifically activated Erk signalling in the zebrafish telencephalon. While CB1 agonist THC did not affect behavioural performance of animals in the colour discrimination paradigm, spatial memory was significantly impaired. The effect of THC on spatial learning is probably specific, since neither motor activity nor anxiety-related behaviour was influenced by the drug treatment. That indicates a striking influence of the endocannabinoid system (ECS) on spatial cognition in zebrafish. Conclusions: The results are very coincident with reports on mammals, demonstrating that the ECS is functional highly conserved during vertebrate evolution. We further conclude that the zebrafish provides a promising model organism for ongoing research on the ECS.