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Pharmacological analysis of zebrafish lphn3.1 morphant larvae suggests that saturated dopaminergic signaling could underlie the ADHD-like locomotor hyperactivity.

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journal contribution
posted on 23.04.2018, 14:04 by M. Lange, C. Froc, H. Grunwald, William H.J. Norton, L. Bally-Cuif
Polymorphisms in the gene coding for the adhesion G-protein coupled receptor LPHN3 are a risk factor for attention-deficit/hyperactivity disorder (ADHD). Transient down-regulation of latrophilin3.1 (lphn3.1), the zebrafish LPHN3 homologue, causes hyperactivity. Zebrafish injected with a lphn3.1-specific morpholino are hyperactive and display an impairment in dopaminergic neuron development. In the present study we used lphn3.1 morphants to further characterize the changes to dopaminergic signaling that trigger hyperactivity. We applied dopamine agonists (Apomorphine, Quinpirole, SKF-38393) and antagonists (Haloperidol, Eticlopride, SCH-23390) to Lphn3.1 morpholino-injected or control-injected animals. The percentage of change in locomotor activity was then determined at three different time periods (10-20 min, 30-40 min and 60-70 min). Our results show that drugs targeting dopamine receptors appear to elicit similar effects on locomotion in zebrafish larvae and mammals. In addition, we observed that lphn3.1 morphants have an overall hyposensitivity to dopamine agonists and antagonists compared to control fish. These results are compatible with a model whereby dopaminergic neurotransmission is saturated in lphn3.1 morphants.

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Citation

Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2018, 84 (Part A), pp. 181-189

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/Biological Sciences/Neuroscience, Psychology and Behaviour

Version

VoR (Version of Record)

Published in

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Publisher

Elsevier

issn

0278-5846

eissn

1878-4216

Acceptance date

22/02/2018

Copyright date

2018

Available date

23/04/2018

Publisher version

https://www.sciencedirect.com/science/article/pii/S0278584617307339?via=ihub#!

Language

en

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