Reversal of dopamine D2 receptor responses by an anandamide transport inhibitor

215Citations
Citations of this article
125Readers
Mendeley users who have this article in their library.

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.

References Powered by Scopus

Isolation and structure of a brain constituent that binds to the cannabinoid receptor

4972Citations
N/AReaders
Get full text

Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides

1900Citations
N/AReaders
Get full text

SR141716A, a potent and selective antagonist of the brain cannabinoid receptor

1665Citations
N/AReaders
Get full text

Cited by Powered by Scopus

The molecular logic of endocannabinoid signalling

1703Citations
N/AReaders
Get full text

Role of endogenous cannabinoids in synaptic signaling

1316Citations
N/AReaders
Get full text

Brain monoglyceride lipase participating in endocannabinoid inactivation

1204Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

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. https://doi.org/10.1523/jneurosci.20-09-03401.2000

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 48

60%

Professor / Associate Prof. 15

19%

Researcher 15

19%

Lecturer / Post doc 2

3%

Readers' Discipline

Tooltip

Agricultural and Biological Sciences 29

38%

Medicine and Dentistry 23

30%

Neuroscience 16

21%

Psychology 9

12%

Save time finding and organizing research with Mendeley

Sign up for free