Dopamine activation of endogenous cannabinoid signaling in dorsal striatum.
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.
Giuffrida
A
A
Department of Pharmacology, University of California at Irvine, 92697-4625, USA.
Parsons
L H
LH
Kerr
T M
TM
Rodríguez de Fonseca
F
F
Navarro
M
M
Piomelli
D
D
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000577:Amides; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D063388:Endocannabinoids; D004983:Ethanolamines / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D005989:Glycerides / Q000494:pharmacology; D006948:Hyperkinesis / Q000139:chemically induced; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009829:Oleic Acids; D010169:Palmitic Acids / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011188:Potassium / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D020891:Raclopride; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000502:physiology; D011955:Receptors, Drug / Q000187:drug effects* / Q000502:physiology; D000077285:Rimonabant; D012457:Salicylamides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D016037:Single-Blind Method; D012964:Sodium / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D000577:Amides; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D063388:Endocannabinoids; D004983:Ethanolamines; D005989:Glycerides; D009829:Oleic Acids; D010169:Palmitic Acids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D017448:Receptors, Dopamine D2; D011955:Receptors, Drug; D012457:Salicylamides; C033595:N-oleoylethanolamine; D019257:Quinpirole; D020891:Raclopride; D013779:Tetrodotoxin; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C005958:palmidrol; C094503:glyceryl 2-arachidonate; D012964:Sodium; D000077285:Rimonabant; D011188:Potassium; D002118:Calcium; C078814:anandamide; D004298:Dopamine