Effect of JWH-250, JWH-073 and their interaction on "tetrad", sensorimotor, neurological and neurochemical responses in mice.

摘要: JWH-250 and JWH-073 are two synthetic cannabinoid agonists with nanomolar affinity at CB1 CB2 receptors. They illegally marketed within "herbal blend" for theirs psychoactive effects greater than those produced by Cannabis. Recently, we analyzed an "herbal" preparation containing a mixture of both JWH-073. The present study was aimed investigating the in vitro vivo pharmacological activity male CD-1 mice. In competition binding experiments performed on mouse human receptors revealed potency studies showed that JWH-073, administered separately, induced marked hypothermia, increased pain threshold to noxious mechanical thermal stimuli, caused catalepsy, reduced motor activity, impaired sensorimotor responses (visual, acoustic tactile), seizures, myoclonia, hyperreflexia promote aggressiveness Moreover, microdialysis freely moving mice systemic administration stimulated dopamine release nucleus accumbens dose-dependent manner. Behavioral, neurological neurochemical were fully prevented selective receptor antagonist/inverse agonist AM 251. Co-administration ineffective doses visual responses, improved mesolimbic DA transmission mice, living unchanged all other behavioral physiological parameters. For first time demonstrates overall it reveals their potentially synergistic action suggesting co-administration different cannabinoids may potentiate detrimental individual compounds increasing dangerousness abuse potential.