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 of the last two neurotrans-mitters, a direct action is possible since GABAergic and glutamatergic neurons in the basal ganglia contain CB1 receptors located presynaptically (see Fig. 1). This enables endocannabinoids to directly influence presynaptic events, such as synthesis, release, or reuptake (see Fernandez-Ruiz et al. 2002 for a review). In contrast, dopaminergic neurons do not contain CB1 receptors (Herkenham et al. 1991b). However, these receptors are abundantly expressed in the caudate-putamen, which is innervated by dopamine-releasing neurons (Herkenham et al. 1991a; Mailleux and Vanderhaeghen 1992a; Tsou et al. 1998a), thus allowing an indirect interaction. In addition, recent data showing that VR1 receptors present in the basal ganglia are likely located in nigrostriatal dopaminergic neurons (Mezey et al. 2000) open up the possibility that some cannabinoids may have a direct effect on dopaminergic transmission (de Lago et al. 2004b).
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