A role for vanilloid receptor 1 (TRPV1) and endocannabinnoid signalling in the regulation of spontaneous and L-DOPA induced locomotion in normal and reserpine-treated rats.
Although most commonly associated with actions at cannabinoid CB1 receptors on the extracellular surface of the plasma membrane, the endocannabinoid anandamide (AEA) is also transported into the cell, by the putative anandamide membrane transporter (AMT), and activates the vanilloid receptor 1 (TRPV1) at an intracellular site. AEA is then inactivated by fatty acid amide hydrolase (FAAH). As systemic administration of TRPV1 ligands reduces locomotor activity in normal rodents, we hypothesised that activation of TRPV1 by endocannabinoids could play a role in the control of voluntary movement and that such actions could be regulated by AMT and FAAH. Motor activity was assessed in normal, in reserpine-treated, and in reserpine-treated rats treated with L-DOPA. In normal rats, the TRPV1 agonist capsaicin (1 mg/kg) or the FAAH inhibitor URB597 (10 mg/kg) caused a significant reduction in movement in both the horizontal (locomotion) and vertical (rearing) planes (-45% and -53% respectively with capsaicin; -33% and -37% for URB597). Capsaicin-induced hypolocomotion was attenuated by the TRPV1 antagonist, capsazepine. There was no effect of capsaicin, URB597 or the AMT inhibitor OMDM-2 on motor activity in reserpine-treated rats. L-DOPA treatment of reserpine-treated rats elicited high levels of motor activity in both the horizontal and vertical planes. Horizontal activity was attenuated by capsaicin (1 mg/kg, -60%), but not by URB597 (10 mg/kg) or OMDM-2 (5 mg/kg). Vertical activity was attenuated by capsaicin (1 mg/kg, -61%) and by URB597 (10 mg/kg, -54%), but not by OMDM-2. These data suggest that activation of the TRPV1 system can suppress spontaneous locomotion in normal animals and modulates several L-DOPA-induced behaviours in reserpine-treated rats.
Lee
Joohyung
J
Toronto Western Research Institute, Toronto Western Hospital, University Health Network, 399 Bathurst Street, MC 11-419, Toronto, Ontario, M5T 2S8, Canada.
Di Marzo
Vincenzo
V
Brotchie
Jonathan M
JM
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology; D001593:Benzyl Compounds / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000037:antagonists & inhibitors / Q000502:physiology*; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000502:physiology*
D018759:Adrenergic Uptake Inhibitors; D001095:Arachidonic Acids; D001549:Benzamides; D001593:Benzyl Compounds; D063385:Cannabinoid Receptor Modulators; D002219:Carbamates; D015259:Dopamine Agents; D004791:Enzyme Inhibitors; C474343:OMDM-2 cpd; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; D007980:Levodopa; D012110:Reserpine; C071423:capsazepine; D002211:Capsaicin