scholarly journals Phenotype-based screening of synthetic cannabinoids in a Dravet Syndrome zebrafish model

2019 ◽  
Author(s):  
Aliesha Griffin ◽  
Mana Anvar ◽  
Kyla Hamling ◽  
Scott C. Baraban

Dravet syndrome (DS) is a catastrophic epilepsy of childhood, characterized by cognitive impairment, severe seizures and increased risk for sudden unexplained death in epilepsy (SUDEP). Although refractory to conventional antiepileptic drugs, emerging preclinical and clinical evidence suggests that modulation of the endocanniboid system could be therapeutic in these patients. Here we used a validated zebrafish model of DS, scn1lab homozygous mutants, to screen a commercially available library containing 370 synthetic cannabinoid (SC) compounds for compounds effective in reducing spontaneous seizures. Primary phenotype-based screening was performed using a locomotion-based assay in 96-well plates, and a secondary local field potential recording assay was then used to confirm suppression of electrographic epileptiform events. Identified SCs with anti-seizure activity, in both assays, included five SCs structurally classified as indole-based cannabinoids: JWH 018 N-(5-chloropentyl) analog, JWH 018 N-(2-methylbutyl) isomer, 5-fluoro PB-22 5-hydroxyisoquinoline isomer, 5-fluoro ADBICA, and AB-FUBINACA 3-fluorobenzyl isomer. Our approach demonstrates that two-stage phenotype-based screening in a zebrafish model of DS successfully identifies synthetic cannabinoids with anti-seizure activity, and supports further investigation of SCs for refractory epilepsies.

2015 ◽  
Vol 8 (2) ◽  
pp. 380
Author(s):  
M.A.J. Lourens ◽  
M.F. Contarino ◽  
R. Verhagen ◽  
P. van den Munckhof ◽  
P.R. Schuurman ◽  
...  

2003 ◽  
Vol 358 (1432) ◽  
pp. 617-620 ◽  
Author(s):  
Terje Lømo

This paper describes circumstances around the discovery of long-term potentiation (LTP). In 1966, I had just begun independent work for the degree of Dr medicinae (PhD) in Per Andersen's laboratory in Oslo after an eighteen-month apprenticeship with him. Studying the effects of activating the perforant path to dentate granule cells in the hippocampus of anaesthetized rabbits, I observed that brief trains of stimuli resulted in increased efficiency of transmission at the perforant path-granule cell synapses that could last for hours. In 1968, Tim Bliss came to Per Andersen's laboratory to learn about the hippocampus and field potential recording for studies of possible memory mechanisms. The two of us then followed up my preliminary results from 1966 and did the experiments that resulted in a paper that is now properly considered to be the basic reference for the discovery of LTP.


Sign in / Sign up

Export Citation Format

Share Document