HEP (2005) 168:479–507
©cSpringer-Verlag 2005
Cannabinoid Control of Motor Function at the Basal Ganglia
J. Fernández-Ruiz () · S. González
Departamento de Bioquímica y Biología Molecular III, Facultad de Medicina,
Universidad Complutense, Ciudad Universitaria s/n, 28040 Madrid, Spain
[email protected]
1 Function of the Endocannabinoid Signaling System in Motor Regions .... 480
1.1 MotorEffectsofCannabinoid-BasedCompounds................ 481
1.1.1 Effects of Plant-Derived, Synthetic, or Endogenous Cannabinoid Agonists.. 481
1.1.2EffectsofInhibitorsofEndocannabinoidInactivation ............. 483
1.1.3EffectsofCannabinoidReceptorAntagonists .................. 483
1.2 Control of Different Neurotransmitters by Cannabinoids in Motor Regions.. 484
1.2.1 γ-AminobutyricAcid ............................... 485
1.2.2Glutamate ..................................... 486
1.2.3Dopamine ..................................... 486
1.3 Presence of Elements of the Endocannabinoid System in Motor Regions... 487
1.3.1CannabinoidandVanilloidReceptors ...................... 487
1.3.2EndocannabinoidLigands ............................ 489
1.3.3EndocannabinoidInactivation .......................... 489
2 Potential Therapeutic Applications of Cannabinoids in Motor Disorders... 490
2.1 GeneralAspects .................................. 490
2.2 Huntington’sDisease ............................... 491
2.2.1ChangesinEndocannabinoidTransmission................... 491
2.2.2TherapeuticUsefulnessofCannabinoids..................... 492
2.3 Parkinson’sDisease ................................ 495
2.3.1ChangesintheEndocannabinoidTransmission................. 496
2.3.2TherapeuticUsefulnessofCannabinoids..................... 497
2.4 OtherMotorDisorders .............................. 498
3 Concluding Remarks and Future Perspectives.................. 499
References ........................................ 500
AbstractClassic and novel data strengthen the idea of a prominent role for the
endocannabinoid signaling system in the control of movement. This finding is sup-
ported by three-fold evidence: (1) the abundance of the cannabinoid CB 1 receptor
subtype, but also of CB 2 and vanilloid VR1 receptors, as well as of endocannabi-
noids in the basal ganglia and the cerebellum, the areas that control movement;
(2) the demonstration of a powerful action, mostly of an inhibitory nature, of
plant-derived, synthetic, and endogenous cannabinoids on motor activity, exerted
by modulating the activity of various classic neurotransmitters; and (3) the occur-
rence of marked changes in endocannabinoid transmission in the basal ganglia
of humans affected by several motor disorders, an event corroborated in animal