| Résumé | Activation of cannabinoid receptor 1 (CB₁) inhibits synaptic transmission in hippocampal
neurons. The goal of this study was to evaluate the ability of benchmark and emerging synthetic
cannabinoids to suppress neuronal activity in vitro using two complementary techniques, Ca²⁺
spiking and multi-electrode arrays (MEAs). Neuron culture and fluorescence imaging conditions
were extensively optimized to provide maximum sensitivity for detection of suppression of
neural activity by cannabinoids. The neuronal Ca²⁺ spiking frequency was significantly
suppressed within 10 min by the prototypic aminoalkylindole cannabinoid, WIN 55,212-2 (10
μM). Suppression by WIN 55,212-2 was not improved by pharmacological intervention with
signaling pathways known to interfere with CB₁ signaling. The naphthoylindole CB₁ agonist,
JWH-018 suppressed Ca²⁺ spiking at a lower concentration (2.5 μM), and the CB₁ antagonist
rimonabant (5 μM), reversed this suppression. In the MEA assay, the ability of synthetic CB₁
agonists to suppress spontaneous electrical activity of hippocampal neurons was evaluated over
80 min sessions. All benchmark (WIN 55,212-2, HU-210, CP 55,940 and JWH-018) and
emerging synthetic cannabinoids (XLR-11, JWH-250, 5F-PB-22, AB-PINACA and MAM-2201)
suppressed neural activity at a concentration of 10 μM; furthermore, several of these compounds
also significantly suppressed activity at 1 μM concentrations. Rimonabant partially reversed
spiking suppression of 5F-PB-22 and, to a lesser extent, of MAM-2201, supporting CB₁-
mediated involvement, although the inactive WIN 55,212-3 also partially suppressed activity.
Taken together, synthetic cannabinoid CB₁-mediated suppression of neuronal activity was
detected using Ca²⁺ spiking and MEAs. |
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