Cannabinoid receptors and their endogenous ligands have been recently identified in the brain as potent inhibitors of neurotransmitter release. Here we show that, in a rat model of Parkinson's disease induced by unilateral nigral lesion with 6-hydroxydopamine (6-OHDA), the striatal levels of anandamide, but not that of the other endocannabinoid 2-arachidonoylglycerol, were increased. Moreover, we observed a decreased activity of the anandamide membrane transporter (AMT) and of the anandamide hydrolase [fatty acid amide hydrolase (FAAH)], whereas the binding of anandamide to cannabinoid receptors was unaffected. Spontaneous glutamatergic activity recorded from striatal spiny neurons was higher in 6-OHDA-lesioned rats. Inhibition of AMT by N-(4-hydroxyphenyl)-arachidonoylamide (AM-404) or by VDM11, or stimulation of the cannabinoid CB1 receptor by HU-210 reduced glutamatergic spontaneous activity in both naive and 6-OHDA-lesioned animals to a similar extent. Conversely, the FAAH inhibitors phenylmethylsulfonyl fluoride and methyl-arachidonoyl fluorophosphonate were much more effective in 6-OHDA-lesioned animals. The present study shows that inhibition of anandamide hydrolysis might represent a possible target to decrease the abnormal cortical glutamatergic drive in Parkinson's disease.

Gubellini, P., Picconi, B., Bari, M., Battista, N., Calabresi, P., Centonze, D., et al. (2002). Experimental parkinsonism alters endocannabinoid degradation: implications for striatal glutamatergic transmission. THE JOURNAL OF NEUROSCIENCE, 22(16), 6900-6907.

Experimental parkinsonism alters endocannabinoid degradation: implications for striatal glutamatergic transmission

CALABRESI, PAOLO;CENTONZE, DIEGO;BERNARDI, GIORGIO;MACCARRONE, MAURO
2002-08-15

Abstract

Cannabinoid receptors and their endogenous ligands have been recently identified in the brain as potent inhibitors of neurotransmitter release. Here we show that, in a rat model of Parkinson's disease induced by unilateral nigral lesion with 6-hydroxydopamine (6-OHDA), the striatal levels of anandamide, but not that of the other endocannabinoid 2-arachidonoylglycerol, were increased. Moreover, we observed a decreased activity of the anandamide membrane transporter (AMT) and of the anandamide hydrolase [fatty acid amide hydrolase (FAAH)], whereas the binding of anandamide to cannabinoid receptors was unaffected. Spontaneous glutamatergic activity recorded from striatal spiny neurons was higher in 6-OHDA-lesioned rats. Inhibition of AMT by N-(4-hydroxyphenyl)-arachidonoylamide (AM-404) or by VDM11, or stimulation of the cannabinoid CB1 receptor by HU-210 reduced glutamatergic spontaneous activity in both naive and 6-OHDA-lesioned animals to a similar extent. Conversely, the FAAH inhibitors phenylmethylsulfonyl fluoride and methyl-arachidonoyl fluorophosphonate were much more effective in 6-OHDA-lesioned animals. The present study shows that inhibition of anandamide hydrolysis might represent a possible target to decrease the abnormal cortical glutamatergic drive in Parkinson's disease.
15-ago-2002
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/26 - NEUROLOGIA
English
Con Impact Factor ISI
Corpus Striatum; Cannabinoids; Glycerides; Rats, Wistar; Hydrolysis; Rats; Endocannabinoids; Receptors, Cannabinoid; Animals; Carrier Proteins; Arachidonic Acids; Patch-Clamp Techniques; Oxidopamine; Glutamic Acid; Disease Models, Animal; Enzyme Inhibitors; Membrane Potentials; Tetrahydrocannabinol; Neurons; Receptors, Drug; Amidohydrolases; Polyunsaturated Alkamides; Parkinsonian Disorders; Synaptic Transmission
Gubellini, P., Picconi, B., Bari, M., Battista, N., Calabresi, P., Centonze, D., et al. (2002). Experimental parkinsonism alters endocannabinoid degradation: implications for striatal glutamatergic transmission. THE JOURNAL OF NEUROSCIENCE, 22(16), 6900-6907.
Gubellini, P; Picconi, B; Bari, M; Battista, N; Calabresi, P; Centonze, D; Bernardi, G; Finazzi Agrò, A; Maccarrone, M
Articolo su rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/50349
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