Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice.
Catherine Ledent, Olga Valverde, G Cossu, F Petitet, J F Aubert, F Beslot, G A Böhme, A Imperato, T Pedrazzini, B P Roques, G Vassart, W Fratta, Marc Parmentier
Science (New York, N.Y.) January 15, 1999 DOI: 10.1126/science.283.5400.401 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study (gene knockout in mice) Peer reviewed |
|---|---|
| Population | Mutant mice with invalidated CB1 receptor gene |
| Key findings | Mutant mice lacking CB1 receptors showed no responses to cannabinoid drugs, while acute opiate effects were unaffected. Morphine reinforcement and withdrawal severity were strongly reduced, indicating CB1's role in opiate motivational properties and physical dependence. |
Abstract
The function of the central cannabinoid receptor (CB1) was investigated by invalidating its gene. Mutant mice did not respond to cannabinoid drugs, demonstrating the exclusive role of the CB1 receptor in mediating analgesia, reinforcement, hypothermia, hypolocomotion, and hypotension. The acute effects of opiates were unaffected, but the reinforcing properties of morphine and the severity of the withdrawal syndrome were strongly reduced. These observations suggest that the CB1 receptor is involved in the motivational properties of opiates and in the development of physical dependence and extend the concept of an interconnected role of CB1 and opiate receptors in the brain areas mediating addictive behavior.