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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) An erratum has been published 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 (115) Citing Articles via Google Scholar Google Scholar Articles by Beltramo, M. Articles by Piomelli, D. Search for Related Content PubMed PubMed Citation Articles by Beltramo, M. Articles by Piomelli, D. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

 Previous Article  |  Next Article 

The Journal of Neuroscience, May 1, 2000, 20(9):3401-3407

Reversal of Dopamine D₂ Receptor Responses by an Anandamide Transport Inhibitor

Massimiliano Beltramo¹, Fernando Rodríguez de Fonseca², Miguel Navarro², Antonio Calignano⁴, Miguel Angel Gorriti², Gerasimos Grammatikopoulos⁵, Adolfo G. Sadile⁵, Andrea Giuffrida³, and Daniele Piomelli¹

¹ The Neurosciences Institute, San Diego, CA 92121, ² Department of Psychobiology, Complutense University, Madrid, Spain 28233, ³ Department of Pharmacology, University of Naples, Italy, 80131, ⁴ Laboratory of Neurophysiology, Behavior and Neural Networks, II University of Naples, Italy, 80138, and ⁵ Department of Pharmacology, University of California, Irvine, California 92697-4625

We characterized the pharmacological properties of the anandamide transport inhibitor N-(4-hydroxyphenyl)-arachidonamide (AM404) in rats and investigated the effects of this drug on behavioral responses associated with activation of dopamine D₂ family receptors. Rat brain slices accumulated [³H]anandamide via a high-affinity transport mechanism that was blocked by AM404. When administered alone in vivo, AM404 caused a mild and slow-developing hypokinesia that was significant 60 min after intracerebroventricular injection of the drug and was reversed by the CB1 cannabinoid receptor antagonist SR141716A. AM404 produced no significant catalepsy or analgesia, two typical effects of direct-acting cannabinoid agonists. However, AM404 prevented the stereotypic yawning produced by systemic administration of a low dose of apomorphine, an effect that was dose-dependent and blocked by SR141716A. Furthermore, AM404 reduced the stimulation of motor behaviors elicited by the selective D₂ family receptor agonist quinpirole. Finally, AM404 reduced hyperactivity in juvenile spontaneously hypertensive rats, a putative model of attention deficit hyperactivity disorder. The results support a primary role of the endocannabinoid system in the regulation of psychomotor activity and point to anandamide transport as a potential target for neuropsychiatric medicines.

Key words: AM404; anandamide transport; cannabinoid receptors; dopamine receptors; spontaneously hypertensive rats; Wistar-Kyoto rats

---

Copyright © 2000 Society for Neuroscience  0270-6474/00/2093401-07$05.00/0

This article has been cited by other articles:

				L. Orio, S. Edwards, O. George, L. H. Parsons, and G. F. Koob A Role for the Endocannabinoid System in the Increased Motivation for Cocaine in Extended-Access Conditions J. Neurosci., April 15, 2009; 29(15): 4846 - 4857. [Abstract] [Full Text] [PDF]

				V. Trezza and L. J. M. J. Vanderschuren Divergent Effects of Anandamide Transporter Inhibitors with Different Target Selectivity on Social Play Behavior in Adolescent Rats J. Pharmacol. Exp. Ther., January 1, 2009; 328(1): 343 - 350. [Abstract] [Full Text] [PDF]

				T. Asua, A. Bilbao, M. A. Gorriti, J. A. Lopez-Moreno, M. del Mar Alvarez, M. Navarro, F. Rodriguez de Fonseca, A. Perez-Castillo, and A. Santos Implication of the Endocannabinoid System in the Locomotor Hyperactivity Associated with Congenital Hypothyroidism Endocrinology, May 1, 2008; 149(5): 2657 - 2666. [Abstract] [Full Text] [PDF]

				M. V. Madsen, L. Peacock, T. Werge, and M. B. Andersen Effects of the cannabinoid CB1 receptor agonist CP55,940 and antagonist SR141716A on d-amphetamine-induced behaviours in Cebusmonkeys J Psychopharmacol, September 1, 2006; 20(5): 622 - 628. [Abstract] [PDF]

				G. La Rana, R. Russo, P. Campolongo, M. Bortolato, R. A. Mangieri, V. Cuomo, A. Iacono, G. M. Raso, R. Meli, D. Piomelli, et al. Modulation of Neuropathic and Inflammatory Pain by the Endocannabinoid Transport Inhibitor AM404 [N-(4-Hydroxyphenyl)-eicosa-5,8,11,14-tetraenamide] J. Pharmacol. Exp. Ther., June 1, 2006; 317(3): 1365 - 1371. [Abstract] [Full Text] [PDF]

				M. Andersson, A. Usiello, A. Borgkvist, L. Pozzi, C. Dominguez, A. A. Fienberg, P. Svenningsson, B. B. Fredholm, E. Borrelli, P. Greengard, et al. Cannabinoid Action Depends on Phosphorylation of Dopamine- and cAMP-Regulated Phosphoprotein of 32 kDa at the Protein Kinase A Site in Striatal Projection Neurons J. Neurosci., September 14, 2005; 25(37): 8432 - 8438. [Abstract] [Full Text] [PDF]

				C. S. Kearn, K. Blake-Palmer, E. Daniel, K. Mackie, and M. Glass Concurrent Stimulation of Cannabinoid CB1 and Dopamine D2 Receptors Enhances Heterodimer Formation: A Mechanism for Receptor Cross-Talk? Mol. Pharmacol., May 1, 2005; 67(5): 1697 - 1704. [Abstract] [Full Text] [PDF]

				D. Fegley, S. Kathuria, R. Mercier, C. Li, A. Goutopoulos, A. Makriyannis, and D. Piomelli From the Cover: Anandamide transport is independent of fatty-acid amide hydrolase activity and is blocked by the hydrolysis-resistant inhibitor AM1172 PNAS, June 8, 2004; 101(23): 8756 - 8761. [Abstract] [Full Text] [PDF]

				M. Melis, M. Pistis, S. Perra, A. L. Muntoni, G. Pillolla, and G. L. Gessa Endocannabinoids Mediate Presynaptic Inhibition of Glutamatergic Transmission in Rat Ventral Tegmental Area Dopamine Neurons through Activation of CB1 Receptors J. Neurosci., January 7, 2004; 24(1): 53 - 62. [Abstract] [Full Text] [PDF]

				T. F. FREUND, I. KATONA, and D. PIOMELLI Role of Endogenous Cannabinoids in Synaptic Signaling Physiol Rev, July 1, 2003; 83(3): 1017 - 1066. [Abstract] [Full Text] [PDF]

				R. Gomez, M. Navarro, B. Ferrer, J. M. Trigo, A. Bilbao, I. Del Arco, A. Cippitelli, F. Nava, D. Piomelli, and F. Rodriguez de Fonseca A Peripheral Mechanism for CB1 Cannabinoid Receptor-Dependent Modulation of Feeding J. Neurosci., November 1, 2002; 22(21): 9612 - 9617. [Abstract] [Full Text] [PDF]

				P. Gubellini, B. Picconi, M. Bari, N. Battista, P. Calabresi, D. Centonze, G. Bernardi, A. Finazzi-Agro, and M. Maccarrone Experimental Parkinsonism Alters Endocannabinoid Degradation: Implications for Striatal Glutamatergic Transmission J. Neurosci., August 15, 2002; 22(16): 6900 - 6907. [Abstract] [Full Text] [PDF]

				T. P. Dinh, D. Carpenter, F. M. Leslie, T. F. Freund, I. Katona, S. L. Sensi, S. Kathuria, and D. Piomelli Brain monoglyceride lipase participating in endocannabinoid inactivation PNAS, August 6, 2002; 99(16): 10819 - 10824. [Abstract] [Full Text] [PDF]

				A. Giuffrida, M. Beltramo, and D. Piomelli Mechanisms of Endocannabinoid Inactivation: Biochemistry and Pharmacology J. Pharmacol. Exp. Ther., July 1, 2001; 298(1): 7 - 14. [Abstract] [Full Text]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help