PT - JOURNAL ARTICLE AU - Paolo Gubellini AU - Barbara Picconi AU - Monica Bari AU - Natalia Battista AU - Paolo Calabresi AU - Diego Centonze AU - Giorgio Bernardi AU - Alessandro Finazzi-Agrò AU - Mauro Maccarrone TI - Experimental Parkinsonism Alters Endocannabinoid Degradation: Implications for Striatal Glutamatergic Transmission AID - 10.1523/JNEUROSCI.22-16-06900.2002 DP - 2002 Aug 15 TA - The Journal of Neuroscience PG - 6900--6907 VI - 22 IP - 16 4099 - http://www.jneurosci.org/content/22/16/6900.short 4100 - http://www.jneurosci.org/content/22/16/6900.full SO - J. Neurosci.2002 Aug 15; 22 AB - 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 byN-(4-hydroxyphenyl)-arachidonoylamide (AM-404) or by VDM11, or stimulation of the cannabinoid CB1 receptor by HU-210 reduced glutamatergic spontaneous activity in both naı̈ve 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.