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Cannabinoids inhibit the synaptic uptake of adenosine and dopamine in the rat and mouse striatum

Cannabinoids inhibit the synaptic uptake of adenosine and dopamine in the rat and mouse striatum

  1. Anonymous
    Eur. J. Pharmacol. (2011), doi:10.1016/j.ejphar.2011.01.013

    Pandolfo et al.

    Abstract
    Adenosine, dopamine and endocannabinoids strictly modulate the release of one another in the dorsolateral striatum thereby controlling synaptic plasticity. As a second level of interaction, they regulate the action of one another via receptor heteromer formation. Here we investigated a putative third level of interaction, i.e. the possible control by cannabinoids of synaptic dopamine and adenosine reuptake. We found that a large number of endo- and exogenous cannabinoid ligands inhibit the uptake of [3H]adenosine and [3H]dopamine in rat sriatal nerve terminals. Maximal effects were often comparable to those of the dopamine transporter inhibitor, GBR12783 and the equilibrative nucleoside transporter inhibitor, dipyridamole. Cannabinoid ligands were generally more potent to inhibit the uptake of adenosine than that of dopamine. The inhibitory effect was: (1) unrelated to the pharmacological profile(s) of the ligands at the cannabinoid CB1, CB2, GPR55 and at the vanilloid TRPV1 receptors; (2) not prevented by the cannabinoid CB1 receptor antagonist/inverse agonist, LY320135; and (3) maintained in the cannabinoid CB1 receptor knockout mice. In the same experiments, only O-2050, cannabidiol, and WIN55212-3 inhibited the simultaneously measured DL-TBOA sensitive uptake of [14C]glutamate. In summary, many cannabinoid ligands are able to inhibit the synaptic uptake of adenosine and dopamine. These effects are not mediated by cannabinoid CB1 receptors, and should be an additional mechanism to consider when interpreting synaptic effects of cannabinoids.