Original articleEndocannabinoids Activate Transient Receptor Potential Vanilloid 1 Receptors to Reduce Hyperdopaminergia-Related Hyperactivity: Therapeutic Implications
Section snippets
Animals
Dopamine transporter wild-type (WT), heterozygous (HZ), and KO mice of the B6xD2F1 background were used in this study. Breeding, genotyping, and maintenance of the mice were as previously described (Morice et al 2005). All experiments were carried out in accordance with the European Communities Council Directive (86/809/EEC) regarding the care and use of animals for experimental procedures and approved by the local ethical committee.
Drugs
The AM251and AM404 (both from Tocris, Illkirch, France) and
Region-Specific Modulation of Anandamide Levels in DAT KO Mice
Tissue levels of the major endocannabinoid anandamide were measured in the hippocampus, cortex, cerebellum, and striatum of DAT WT, HZ, and KO mice. We show that in DAT KO mice, anandamide levels were significantly reduced by 30%, specifically in the striatum [F(2,35) = 3.85, p < .05; Figure 1]. No difference in anandamide levels was seen in the other regions tested (Figure 1).
The Cannabinoid Antagonist AM251 Does Not Affect Locomotion in the DAT KO Mice
Cannabinoid type 1 receptor antagonists have been shown to effectively attenuate psychostimulant-induced
Discussion
In the present study, we investigated the interactions between dopamine and endocannabinoid systems using a well-established animal model of hyperdopaminergia, the DAT KO mice. The tissue levels of the major endocannabinoid anandamide were measured in the hippocampus, cortex, cerebellum, and striatum of DAT WT, HZ, and KO mice. In the DAT KO mice, anandamide levels were significantly diminished, specifically in the striatum, the forebrain dopamine nerve terminal region, which has been
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