Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice

摘要: Δ9-Tetrahydrocannabinol (Δ9-THC), the major psychoactive ingredient in preparations of Cannabis sativa (marijuana, hashish), elicits central nervous system (CNS) responses, including cognitive alterations and euphoria. These responses account for abuse potential cannabis, while other effects such as analgesia suggest medicinal applications. To study role known target cannabinoids CNS, CB1 cannabinoid receptor, we have produced a mouse strain with disrupted gene. knockout mice appeared healthy fertile, but they had significantly increased mortality rate. They also displayed reduced locomotor activity, ring catalepsy, hypoalgesia hotplate formalin tests. Δ9-THC-induced ring-catalepsy, hypomobility, hypothermia were completely absent mutant mice. In contrast, still found tail-flick test behavioral (licking abdomen) physiological (diarrhea) after Δ9-THC administration. Thus, most, not all, CNS are mediated by receptor.