QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 16, 2005, 25(11):2874-2884; doi:10.1523/JNEUROSCI.4232-04.2005

This Article Full Text Full Text (PDF) Supplemental data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (66) Citing Articles via Google Scholar Google Scholar Articles by Köfalvi, A. Articles by Sperlágh, B. Search for Related Content PubMed PubMed Citation Articles by Köfalvi, A. Articles by Sperlágh, B.

 Previous Article  |  Next Article 

Cellular/Molecular
Involvement of Cannabinoid Receptors in the Regulation of Neurotransmitter Release in the Rodent Striatum: A Combined Immunochemical and Pharmacological Analysis

Attila Köfalvi,^1,2 Ricardo J. Rodrigues,² Catherine Ledent,³ Ken Mackie,⁴ E. Sylvester Vizi,¹ Rodrigo A. Cunha,² and Beáta Sperlágh¹

¹Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1450, Hungary, ²Center for Neuroscience of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal, ³Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Brussels B-1070, Belgium, and ⁴Department of Anesthesiology and Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195

Despite the profound effect of cannabinoids on motor function, and their therapeutic potential in Parkinson's and Huntington's diseases, the cellular and subcellular distributions of striatal CB₁ receptors are not well defined. Here, we show that CB₁ receptors are primarily located on GABAergic (vesicular GABA transporter-positive) and glutamatergic [vesicular glutamate transporter-1 (VGLUT-1)- and VGLUT-2-positive] striatal nerve terminals and are present in the presynaptic active zone, in the postsynaptic density, as well as in the extrasynaptic membrane. Both the nonselective agonist WIN552122 [(R)-(+)-[2,3-dihydro-5-methyl-3[(4-morpholinyl)methyl] pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate salt] (EC₅₀, 32 nM) and the CB₁-selective agonist ACEA [N-(2-chloroethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide] inhibited [³H]GABA release from rat striatal slices. The effect of these agonists was prevented by the CB₁-selective antagonists SR141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide] (1 µM) and AM251 [1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide trifluoroacetate salt] (1 µM), indicating that cannabinoids inhibit the release of GABA via activation of presynaptic CB₁ receptors. Cannabinoids modulated glutamate release via both CB₁ and non-CB₁ mechanisms. Cannabinoid agonists and antagonists inhibited 25 mM K⁺-evoked [³H]glutamate release and sodium-dependent [³H]glutamate uptake. Partial involvement of CB₁ receptors is suggested because low concentrations of SR141716A partly and AM251 fully prevented the effect of WIN552122 and CP55940 [5-(1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]phenol]. However, the effect of CB₁ agonists and antagonists persisted in CB₁ knock-out mice, indicating the involvement of non-CB₁,CB₁-like receptors. In contrast, cannabinoids did not modulate [³H]dopamine release or [³H]dopamine and [³H]GABA uptake. Our results indicate distinct modulation of striatal GABAergic and glutamatergic transmission by cannabinoids and will facilitate the understanding of the role and importance of the cannabinoid system in normal and pathological motor function.

Key words: striatum; cannabinoid; CB₁ receptor; knock-out; GABA; glutamate; dopamine; release

---

Received Oct 12, 2004; revised January 25, 2005; accepted January 25, 2005.

This article has been cited by other articles:

				P. D. Morrison and R. M. Murray From Real-World Events to Psychosis: The Emerging Neuropharmacology of Delusions Schizophr Bull, July 1, 2009; 35(4): 668 - 674. [Abstract] [Full Text] [PDF]

				B. Gonzalez, F. Paz, L. Floran, J. Aceves, D. Erlij, and B. Floran Cannabinoid Agonists Stimulate [3H]GABA Release in the Globus Pallidus of the Rat When Gi Protein-Receptor Coupling Is Restricted: Role of Dopamine D2 Receptors J. Pharmacol. Exp. Ther., March 1, 2009; 328(3): 822 - 828. [Abstract] [Full Text] [PDF]

				D. Ryan, A. J. Drysdale, C. Lafourcade, R. G. Pertwee, and B. Platt Cannabidiol Targets Mitochondria to Regulate Intracellular Ca2+ Levels J. Neurosci., February 18, 2009; 29(7): 2053 - 2063. [Abstract] [Full Text] [PDF]

				K. Van Laere, K. Goffin, G. Bormans, C. Casteels, L. Mortelmans, J. de Hoon, I. Grachev, M. Vandenbulcke, and G. Pieters Relationship of Type 1 Cannabinoid Receptor Availability in the Human Brain to Novelty-Seeking Temperament Arch Gen Psychiatry, February 1, 2009; 66(2): 196 - 204. [Abstract] [Full Text] [PDF]

				A.-G. Corbille, E. Valjent, G. Marsicano, C. Ledent, B. Lutz, D. Herve, and J.-A. Girault Role of Cannabinoid Type 1 Receptors in Locomotor Activity and Striatal Signaling in Response to Psychostimulants J. Neurosci., June 27, 2007; 27(26): 6937 - 6947. [Abstract] [Full Text] [PDF]

				M. Uchigashima, M. Narushima, M. Fukaya, I. Katona, M. Kano, and M. Watanabe Subcellular Arrangement of Molecules for 2-Arachidonoyl-Glycerol-Mediated Retrograde Signaling and Its Physiological Contribution to Synaptic Modulation in the Striatum J. Neurosci., April 4, 2007; 27(14): 3663 - 3676. [Abstract] [Full Text] [PDF]

				A. Degroot, A. Kofalvi, M. R. Wade, R. J. Davis, R. J. Rodrigues, N. Rebola, R. A. Cunha, and G. G. Nomikos CB1 Receptor Antagonism Increases Hippocampal Acetylcholine Release: Site and Mechanism of Action Mol. Pharmacol., October 1, 2006; 70(4): 1236 - 1245. [Abstract] [Full Text] [PDF]

				E. S. Graham, N. Ball, E. L. Scotter, P. Narayan, M. Dragunow, and M. Glass Induction of Krox-24 by Endogenous Cannabinoid Type 1 Receptors in Neuro2A Cells Is Mediated by the MEK-ERK MAPK Pathway and Is Suppressed by the Phosphatidylinositol 3-Kinase Pathway J. Biol. Chem., September 29, 2006; 281(39): 29085 - 29095. [Abstract] [Full Text] [PDF]

				I. Freiman, A. Anton, H. Monyer, M. J. Urbanski, and B. Szabo Analysis of the effects of cannabinoids on identified synaptic connections in the caudate-putamen by paired recordings in transgenic mice J. Physiol., September 15, 2006; 575(3): 789 - 806. [Abstract] [Full Text] [PDF]

				S. R. Laviolette and A. A. Grace Cannabinoids Potentiate Emotional Learning Plasticity in Neurons of the Medial Prefrontal Cortex through Basolateral Amygdala Inputs. J. Neurosci., June 14, 2006; 26(24): 6458 - 6468. [Abstract] [Full Text] [PDF]

				T. Yoshida, M. Fukaya, M. Uchigashima, E. Miura, H. Kamiya, M. Kano, and M. Watanabe Localization of diacylglycerol lipase-alpha around postsynaptic spine suggests close proximity between production site of an endocannabinoid, 2-arachidonoyl-glycerol, and presynaptic cannabinoid CB1 receptor. J. Neurosci., May 3, 2006; 26(18): 4740 - 4751. [Abstract] [Full Text] [PDF]

				Y. Kawamura, M. Fukaya, T. Maejima, T. Yoshida, E. Miura, M. Watanabe, T. Ohno-Shosaku, and M. Kano The CB1 cannabinoid receptor is the major cannabinoid receptor at excitatory presynaptic sites in the hippocampus and cerebellum. J. Neurosci., March 15, 2006; 26(11): 2991 - 3001. [Abstract] [Full Text] [PDF]

				U. Pagotto, G. Marsicano, D. Cota, B. Lutz, and R. Pasquali The Emerging Role of the Endocannabinoid System in Endocrine Regulation and Energy Balance Endocr. Rev., February 1, 2006; 27(1): 73 - 100. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help