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

Abstract : 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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Submitted on : Sunday, December 8, 2019 - 9:34:01 PM
Last modification on : Wednesday, October 14, 2020 - 3:42:02 AM
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Merlin Lange, Cynthia Froc, Hannah Grunwald, William H.J. Norton, Laure Bally-Cuif. Pharmacological analysis of zebrafish lphn3.1 morphant larvae suggests that saturated dopaminergic signaling could underlie the ADHD-like locomotor hyperactivity. Progress in Neuro-Psychopharmacology and Biological Psychiatry, Elsevier, 2018, 84, pp.181-189. ⟨10.1016/j.pnpbp.2018.02.010⟩. ⟨pasteur-02399123⟩

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