HEP (2005) 168:117–145
©cSpringer-Verlag 2005
Analysis of the Endocannabinoid System by Using CB 1
Cannabinoid Receptor Knockout Mice
O. Valverde^1 ·M.Karsak^2 · A. Zimmer^2 ()
(^1) Laboratori de Neurofarmacologia, Departament de Ciències Experimentals i de la Salut,
Universitat Pompeu Fabra, Carrer Dr. Aiguader, 80, 08003 Barcelona, Spain
(^2) Laboratory of Molecular Neurobiology, Clinic of Psychiatry, Neurocenter, University of
Bonn, Sigmund-Freud-Strasse 25, 53105 Germany
[email protected]
1GenerationofCB 1 Knockout Mice ........................ 118
2 Neurochemical and Biochemical Adaptive Changes Produced by the Lack
of the CB 1 Cannabinoid Receptors ........................ 119
3CB 1 Cannabinoid Receptors Participate in the Control of Locomotion .... 120
4CB 1 CannabinoidReceptorsandEmotionalBehaviour............. 121
5CB 1 Cannabinoid Receptors Participate in the Control of Cognitive Functions^122
6CB 1 Cannabinoid Receptors Participate in the Control
of Cardiovascular Responses ........................... 124
7 Participation of the CB 1 Cannabinoid Receptors in the Control of Pain.... 124
8CB 1 CannabinoidReceptorsandAddiction................... 127
9 Interaction Between Cannabinoid Receptors and Other Addictive Drugs... 129
9.1 InteractionBetweenCannabinoidsandOpioids................. 129
9.2 InteractionBetweenCannabinoidsandPsychostimulants ........... 131
9.3 InteractionBetweenCannabinoidsandNicotine ................ 132
9.4 InteractionBetweenCannabinoidsandEthanol ................ 133
10 CB 1 ReceptorsintheControlofFeedingBehaviour .............. 134
11 Endocannabinoid as Retrograde Neurotransmitter .............. 135
12 Outlook ...................................... 136
References ........................................ 137
AbstractThe endocannabinoid system has been involved in the control of several
neurophysiologicalandbehaviouralresponses.Todate,threelinesofCB 1 knockout
mice have been established independently in different laboratories. This chapter
reviews the main results obtained with these lines of CB 1 knockout mice in several
physiological responses that have been previously related to the activity of the en-
docannabinoid system. Studies using CB 1 knockout mice have demonstrated that
this receptor participates in the control of several behavioural responses including
locomotion, anxiety- and depressive-like states, cognitive functions such as mem-
ory and learning processes, cardiovascular responses and feeding. Furthermore,