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Cannabinoids inhibit the synaptic uptake of adenosine and dopamine in the rat and mouse striatum.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2011 Mar 25; Vol. 655 (1-3), pp. 38-45. Date of Electronic Publication: 2011 Jan 23. - Publication Year :
- 2011
-
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 [(3)H]adenosine and [(3)H]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 CB(1), CB(2), GPR55 and at the vanilloid TRPV(1) receptors; (2) not prevented by the cannabinoid CB(1) receptor antagonist/inverse agonist, LY320135; and (3) maintained in the cannabinoid CB(1) receptor knockout mice. In the same experiments, only O-2050, cannabidiol, and WIN55212-3 inhibited the simultaneously measured DL-TBOA-sensitive uptake of [(14)C]glutamate. In summary, many cannabinoid ligands are able to inhibit the synaptic uptake of adenosine and dopamine. These effects are not mediated by cannabinoid CB(1) receptors, and should be an additional mechanism to consider when interpreting synaptic effects of cannabinoids.<br /> (Copyright © 2010 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Biological Transport drug effects
Cannabinoid Receptor Modulators pharmacology
Cannabinoids chemical synthesis
Dopamine Uptake Inhibitors chemical synthesis
Dopamine Uptake Inhibitors pharmacology
Dose-Response Relationship, Drug
Glutamates metabolism
In Vitro Techniques
Ligands
Male
Mice
Neostriatum cytology
Nerve Endings drug effects
Nerve Endings metabolism
Plants chemistry
Rats
Adenosine metabolism
Cannabinoids pharmacology
Dopamine metabolism
Neostriatum drug effects
Neostriatum metabolism
Synapses drug effects
Synapses metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0712
- Volume :
- 655
- Issue :
- 1-3
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 21266173
- Full Text :
- https://doi.org/10.1016/j.ejphar.2011.01.013