Synthetic cannabinoid JWH-073 alters both acute behavior and in vivo/vitro electrophysiological responses in mice

JWH-073 is a synthetic cannabinoid (SCB) that is illegally marketed within an "herbal blend", causing psychoactive effects more intense than those produced by Cannabis. Users report that JWH-073 causes less harmful effects than other SCBs, misrepresenting it as a "safe JWH-018 alternative", which in turn prompts its recreational use. The present study is aimed to investigate the in vivo pharmacological activity on physiological and neurobehavioral parameters in male CD-1 mice after acute 1 mg/kg JWH-073 administration. To this aim we investigate its effect on sensorimotor (visual, acoustic, and tactile), motor (spontaneous motor activity and catalepsy), and memory functions (novel object recognition; NOR) in mice coupling behavioral and EEG data. Moreover, to clarify how memory function is affected by JWH-073, we performed in vitro electrophysiological studies in hippocampal preparations using a Long-Term Potentiation (LTP) stimulation paradigm. We demonstrated that acute administration of JWH-073 transiently decreased motor activity for up to 25 min and visual sensorimotor responses for up to 105 min, with the highest effects at 25 min (similar to 48 and similar to 38%, respectively), while the memory function was altered up to 24h (similar to 33%) in treated-mice as compared to the vehicle. EEG in the somatosensory cortex showed a maximal decrease of alpha (similar to 23%) and gamma (similar to 26%) bands at 15 min, beta (similar to 26%) band at 25 min, a maximal increase of theta (similar to 14%) band at 25 min and delta (similar to 35%) band at 2 h, and a significant decrease of theta (similar to 18%), alpha (similar to 26%), and beta (similar to 10%) bands during 24 h. On the other hand, EEG in the hippocampus showed a significant decrease of all bands from 10 min to 2 h, with the maximal effect at 30 min for theta (similar to 34%) and gamma (similar to 26%) bands and 2 h for alpha (similar to 36%), beta (similar to 29%), and delta (similar to 15%) bands. Notably, the delta band significant increase both at 5 min (similar to 12%) and 24 h (similar to 19%). Moreover, in vitro results support cognitive function impairment (similar to 60% of decrease) by interfering with hippocampal synaptic transmission and LTP generation. Our results suggest that JWH-073 deeply alters brain electrical responsiveness with minor behavioral symptoms. Thus, it poses a subtle threat to consumers who mistakenly consider it safer than other SCBs.