Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice.
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.
Ledent
C
C
IRIBHN, Université libre de Bruxelles, B-1070 Brussels, Belgium.
Valverde
O
O
Cossu
G
G
Petitet
F
F
Aubert
J F
JF
Beslot
F
F
Böhme
G A
GA
Imperato
A
A
Pedrazzini
T
T
Roques
B P
BP
Vassart
G
G
Fratta
W
W
Parmentier
M
M
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002186:Cannabinoids / Q000378:metabolism / Q000494:pharmacology*; D013759:Dronabinol / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000494:pharmacology*; D009293:Opioid-Related Disorders / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000235:genetics / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000502:physiology; D012054:Reinforcement, Psychology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
D000701:Analgesics, Opioid; D002186:Cannabinoids; D009294:Narcotics; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D017473:Receptors, Opioid, kappa; D009020:Morphine; D013759:Dronabinol