Cannabinoid receptor in the basal ganglia

Herkenham M, Lynn AB, De Costa BR, Richfield EK (1991) Neuronal localization of cannabinoid receptors in the basal ganglia of the rat. Brain Res 547 267-274... 

Lastres-Becker I, Gomez M, De Miguel R, Ramos JA, Fernandez-Ruiz J (2002b) Loss of cannabinoid CBI receptors in the basal ganglia in the late akinetic phase of rats with experimental Huntington s disease. Neurotox Res 4 601-608... 

Lastres-Becker 1, Berrendero F, Lucas JJ, Marli n-Aparicio E, Yamamoto A, Ramos JA, Ferndndez-Ruiz J (2002c) Loss of mRNA levels, binding and activation of GTP-binding proteins for cannabinoid CBI receptors in the basal ganglia of a transgenic model of Huntington s disease. Brain Res 929 236-242... 

Cannabinoids might alleviate some parkinsonian symptoms by their remarkable receptor-mediated modulatory action in the basal ganglia output nuclei. Moreover, it was recently observed that some cannabinoids are potent antioxidants that can protect neurons from death even without cannabinoid receptor activation. It seems that cannabinoids could delay or even stop progressive degeneration of brain dopaminergic systems, a process for which there is presently no prevention. 

Mailleux, P., and Vanderhaeghen, J. J. (1992). Localization of cannabinoid receptor in the human developing and adult basal ganglia. Higher levels in the striatonigral neurons. Neurosci. Lett. 148, 173-176. 

The primary active component of cannabis is A9-tetrahy-drocannabinol (THC), which is responsible for the greater part of the pharmacological effects of the cannabis complex. A8-THC is also active. However, the cannabis plant contains more than 400 chemicals, of which some 60 are chemically related to A9-THC, and it is evident that the exact proportions in which these are present can vary considerably, depending on the way in which the material has been harvested and prepared. In man, A9-THC is rapidly converted to 11-hydroxy-A9-THC (5), a metabolite that is active in the central nervous system. A specific receptor for the cannabinols has been identified it is a member of the G-protein-linked family of receptors (6). The cannabinoid receptor is linked to the inhibitory G-protein, which is linked to adenyl cyclase in an inhibitory fashion (7). The cannabinoid receptor is found in highest concentrations in the basal ganglia, the hippocampus, and the cerebellum, with lower concentrations in the cerebral cortex. 

Romero J, Berrendero F, Garcia-GU L, Ramos J, Fernandez-Ruiz J (1998a) Cannabinoid receptor and WlN-55,212-2-stimulated [35SJGTP gamma S binding and cannabinoid receptor mRNA levels in the basal ganglia and the cerebeUum of adult male rats chronically exposed to delta 9-tetrahydrocannabinoL J Mol Neurosci 11 109-119... 

As indicated above, the administration of different cannabinoids impairs movement in rodents and humans. It is expected that this effect depends on the direct or indirect action of cannabinoids on the levels of several neurotransmitters that have been classically involved in the control of basal ganglia function. Three neurotransmitters seem to be influenced by cannabinoids in this circuitry, dopamine, y-aminobutyric acid (GABA), and glutamate. In the case ofthe last two neurotransmitters, a direct action is possible since GABAergic and glutamatergic neurons in the basal ganglia contain CBi receptors located presynaptically (see Fig. 1). This... 

Several studies have addressed the identification and quantification of diverse elements of the endocannabinoid signaling system in the basal ganglia, as a way to establish the importance of the role played by this system in the control of motor function (for a review see Romero et al. 2002). Most of the studies focused on cannabinoid receptors, mainly the CBi subtype and more recently the functionally related receptor subtype, VRl, but some studies have dealt with other key proteins of the endocannabinoid system (for review see Romero et al. 2002). 

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