Abstract
We measured endogenous cannabinoid release in dorsal striatum of freely moving rats by microdialysis and gas chromatography/mass spectrometry. Neural activity stimulated the release of anandamide, but not of other endogenous cannabinoids such as 2-arachidonylglycerol. Moreover, anandamide release was increased eightfold over baseline after local administration of the D2-like (D2, D3, D4) dopamine receptor agonist quinpirole, a response that was prevented by the D2-like receptor antagonist raclopride. Administration of the D1-like (D1, D5) receptor agonist SKF38393 had no such effect. These results suggest that functional interactions between endocannabinoid and dopaminergic systems may contribute to striatal signaling. In agreement with this hypothesis, pretreatment with the cannabinoid antagonist SR141716A enhanced the stimulation of motor behavior elicited by systemic administration of quinpirole. The endocannabinoid system therefore may act as an inhibitory feedback mechanism countering dopamine-induced facilitation of motor activity.
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Acknowledgements
We thank C. Sañudo-Peña, N. Stella and M.J. Walker for comments and discussion. Part of this work was conducted at the Neurosciences Institute and was supported by Neurosciences Research Foundation, which receives major support from Novartis. Additional support was from the National Institute of Drug Abuse (DA12447 and DA12413, to D.P.), CICYT and Plan Nacional sobre Drogas (F.R.F., M.N.). F.R.F. is a research Fellow of the Jaime del Amo Foundation.
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Giuffrida, A., Parsons, L., Kerr, T. et al. Dopamine activation of endogenous cannabinoid signaling in dorsal striatum . Nat Neurosci 2, 358–363 (1999). https://doi.org/10.1038/7268
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DOI: https://doi.org/10.1038/7268
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