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 effectsmore 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) inmice 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 25min and visual sensorimotor responses for up to 105min, with the highest effects at 25min (~48 and ~38%, respectively), while the memory function was altered up to 24 h (~33%) in treated-mice as compared to the vehicle. EEG in the somatosensory cortex showed amaximal decrease of α(~23%) and γ(~26%) bands at 15min, β(~26%) band at 25min, a maximal increase of" (~14%) band at 25min and δ(~35%) band at 2 h, and a significant decrease of θ(~18%), α(~26%), and β(~10%) bands during 24 h. On the other hand, EEG in the hippocampus showed a significant decrease of all bands from 10min to 2 h, with the maximal effect at 30min for θ(~34%) and γ(~26%) bands and 2 h for α(~36%), β(~29%), and δ(~15%) bands. Notably, the d band significant increase both at 5min (~12%) and 24 h (~19%). Moreover, in vitro results support cognitive function impairment (~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. [ABSTRACT FROM AUTHOR]