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

A Zimmer, AM Zimmer, AG Hohmann… - Proceedings of the …, 1999 - National Acad Sciences
A Zimmer, AM Zimmer, AG Hohmann, M Herkenham, TI Bonner
Proceedings of the National Academy of Sciences, 1999National Acad Sciences
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 the abuse
potential of cannabis, while other effects such as analgesia suggest potential medicinal
applications. To study the role of the major known target of cannabinoids in the CNS, the
CB1 cannabinoid receptor, we have produced a mouse strain with a disrupted CB1 gene …
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 the abuse potential of cannabis, while other effects such as analgesia suggest potential medicinal applications. To study the role of the major known target of cannabinoids in the CNS, the CB1 cannabinoid receptor, we have produced a mouse strain with a disrupted CB1 gene. CB1 knockout mice appeared healthy and fertile, but they had a significantly increased mortality rate. They also displayed reduced locomotor activity, increased ring catalepsy, and hypoalgesia in hotplate and formalin tests. Δ9-THC-induced ring-catalepsy, hypomobility, and hypothermia were completely absent in CB1 mutant mice. In contrast, we still found Δ9-THC-induced analgesia in the tail-flick test and other behavioral (licking of the abdomen) and physiological (diarrhea) responses after Δ9-THC administration. Thus, most, but not all, CNS effects of Δ9-THC are mediated by the CB1 receptor.
National Acad Sciences