Reversal of dopamine D2 receptor responses by an anandamide transport inhibitor

Massimiliano Beltramo, Fernando Rodríguez De Fonseca, Miguel Navarro, Antonio Calignano, Miquel Angel Gorriti, Georgios Grammatikopoulos, Adolfo G. Sadile, Andrea Giuffrida, Daniele Piomelli

Research output: Contribution to journalArticle

196 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3401-3407
Number of pages7
JournalJournal of Neuroscience
Volume20
Issue number9
StatePublished - May 1 2000
Externally publishedYes

Fingerprint

Dopamine D2 Receptors
rimonabant
Yawning
Cannabinoid Receptor Antagonists
Cannabinoid Receptor Agonists
Quinpirole
Catalepsy
Endocannabinoids
Hypokinesia
Apomorphine
Inbred SHR Rats
Attention Deficit Disorder with Hyperactivity
anandamide
N-(4-hydroxyphenyl)arachidonylamide
Pharmaceutical Preparations
Analgesia
Pharmacology
Injections
Brain

Keywords

  • AM404
  • Anandamide transport
  • Cannabinoid receptors
  • Dopamine receptors
  • Spontaneously hypertensive rats
  • Wistar-Kyoto rats

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Beltramo, M., Rodríguez De Fonseca, F., Navarro, M., Calignano, A., Gorriti, M. A., Grammatikopoulos, G., ... Piomelli, D. (2000). Reversal of dopamine D2 receptor responses by an anandamide transport inhibitor. Journal of Neuroscience, 20(9), 3401-3407.

Reversal of dopamine D2 receptor responses by an anandamide transport inhibitor. / Beltramo, Massimiliano; Rodríguez De Fonseca, Fernando; Navarro, Miguel; Calignano, Antonio; Gorriti, Miquel Angel; Grammatikopoulos, Georgios; Sadile, Adolfo G.; Giuffrida, Andrea; Piomelli, Daniele.

In: Journal of Neuroscience, Vol. 20, No. 9, 01.05.2000, p. 3401-3407.

Research output: Contribution to journalArticle

Beltramo, M, Rodríguez De Fonseca, F, Navarro, M, Calignano, A, Gorriti, MA, Grammatikopoulos, G, Sadile, AG, Giuffrida, A & Piomelli, D 2000, 'Reversal of dopamine D2 receptor responses by an anandamide transport inhibitor', Journal of Neuroscience, vol. 20, no. 9, pp. 3401-3407.
Beltramo M, Rodríguez De Fonseca F, Navarro M, Calignano A, Gorriti MA, Grammatikopoulos G et al. Reversal of dopamine D2 receptor responses by an anandamide transport inhibitor. Journal of Neuroscience. 2000 May 1;20(9):3401-3407.
Beltramo, Massimiliano ; Rodríguez De Fonseca, Fernando ; Navarro, Miguel ; Calignano, Antonio ; Gorriti, Miquel Angel ; Grammatikopoulos, Georgios ; Sadile, Adolfo G. ; Giuffrida, Andrea ; Piomelli, Daniele. / Reversal of dopamine D2 receptor responses by an anandamide transport inhibitor. In: Journal of Neuroscience. 2000 ; Vol. 20, No. 9. pp. 3401-3407.
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