Dual motor response to l-dopa and nociceptin/orphanin FQ receptor antagonists in 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) treated mice: Paradoxical inhibition is relieved by D(2)/D(3) receptor blockade

Experimental Neurology
Riccardo ViaroMichele Morari

Abstract

Motor activity of mice acutely treated with the parkinsonian toxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) was monitored for 6 days using behavioral tests which provide complementary information on motor function: the bar, reaction time, drag, stair climbing, grip, rotarod and footprinting tests. These tests consistently disclosed a prolonged motor impairment characterized by akinesia, bradykinesia, speed reduction, loss of coordination and gait patterns. This impairment was associated with approximately 60% loss of striatal dopamine terminals, as revealed by tyrosine hydroxylase immunohistochemistry, and was attenuated by dopaminergic drugs. Indeed, the dopamine precursor, l-dopa (1-10 mg/kg), and the D(3)/D(2) receptor agonist pramipexole (0.0001-0.001 mg/kg) promoted stepping activity in the drag test (a test for akinesia/bradykinesia). The novel nociceptin/orphanin FQ receptor (NOP) antagonist 1-[1-(cyclooctylmethyl)-1,2,3,6-tetrahydro-5-(hydroxymethyl)-4-pyridinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (Trap-101, 0.001-0.1 mg/kg), an analogue of 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J-113397), also promoted stepping and synergistically or addit...Continue Reading

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Citations

Feb 26, 2014·The Journal of Physiology·Riccardo ViaroGianfranco Franchi
Jan 16, 2019·Central Nervous System Agents in Medicinal Chemistry·Gokul Krishna Muralidhara
Oct 28, 2019·British Journal of Pharmacology·Daniela MercatelliMichele Morari
Apr 14, 2011·British Journal of Pharmacology·Susan Duty, Peter Jenner
Jul 30, 2018·International Journal of Legal Medicine·Federica FotiFabio De-Giorgio
Dec 28, 2010·Neuropharmacology·Anna RizziGirolamo Calo'
Jun 1, 2021·Translational Neuroscience·Dandong HuJi Zhang

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