Aim: Nociceptin/orphanin FQ (N/OFQ) is an opioid-like neuropeptide which activates a G-protein coupled receptor, the NOP receptor. N/OFQ and its receptor are widely expressed in cerebral areas involved in the control of motor function. In this study we investigated how exogenous and endogenous N/OFQ is able to influence locomotor activity and primary motor cortex (M1) excitability in adult rats. Methods: Ten nmol N/OFQ and 10 nmol UFP-101, a potent and selective NOP receptor peptide antagonist, were injected in the lateral cerebral ventricle. Behavioural test: the rats were tested on the fixed-speed rotarod and rotarod performance calculated 10 and 60 min after drug injection. Electrophysiological recording: movements evoked by intracortical microstimulation (ICMS) of M1 were mapped in each animal under ketamine anaesthesia, starting from 10 min after injection. The ICMS (30ms trains of 0.25ms cathodal pulses at 300Hz, stimulation current *60*A) was delivered at a depth of 1.5mm from the pial surface using glass-insulated tungsten microelectrodes (impedance: 0.6-1.2M*). Results: N/OFQ abolished (~95%) motor activity on the rotarod and increased the mean threshold to evoke vibrissa and forelimb movement (~55% and ~47%, respectively). UFP-101 facilitated motor performance (~75%) and decreased the mean threshold to evoke forelimb movement (~33%). UFP-101 was ineffective in modulating vibrissa threshold. Conclusions: The present results show that activation of NOP receptors impairs motor function and reduces M1 excitability, while blockade of NOP receptors exerts opposite effects. Endogenous N/OFQ drives a tonic inhibitory control on motor behaviour probably by decreasing M1 excitability. Based on our previous findings, N/OFQ action is likely accompleted via subcortical NOP receptors.
Nociceptin/orphanin FQ receptors modulate locomotion and motor cortex excitability in adult Rats
VIARO, Riccardo;MARTI, Matteo;MORARI, Michele;FRANCHI, Gianfranco
2006
Abstract
Aim: Nociceptin/orphanin FQ (N/OFQ) is an opioid-like neuropeptide which activates a G-protein coupled receptor, the NOP receptor. N/OFQ and its receptor are widely expressed in cerebral areas involved in the control of motor function. In this study we investigated how exogenous and endogenous N/OFQ is able to influence locomotor activity and primary motor cortex (M1) excitability in adult rats. Methods: Ten nmol N/OFQ and 10 nmol UFP-101, a potent and selective NOP receptor peptide antagonist, were injected in the lateral cerebral ventricle. Behavioural test: the rats were tested on the fixed-speed rotarod and rotarod performance calculated 10 and 60 min after drug injection. Electrophysiological recording: movements evoked by intracortical microstimulation (ICMS) of M1 were mapped in each animal under ketamine anaesthesia, starting from 10 min after injection. The ICMS (30ms trains of 0.25ms cathodal pulses at 300Hz, stimulation current *60*A) was delivered at a depth of 1.5mm from the pial surface using glass-insulated tungsten microelectrodes (impedance: 0.6-1.2M*). Results: N/OFQ abolished (~95%) motor activity on the rotarod and increased the mean threshold to evoke vibrissa and forelimb movement (~55% and ~47%, respectively). UFP-101 facilitated motor performance (~75%) and decreased the mean threshold to evoke forelimb movement (~33%). UFP-101 was ineffective in modulating vibrissa threshold. Conclusions: The present results show that activation of NOP receptors impairs motor function and reduces M1 excitability, while blockade of NOP receptors exerts opposite effects. Endogenous N/OFQ drives a tonic inhibitory control on motor behaviour probably by decreasing M1 excitability. Based on our previous findings, N/OFQ action is likely accompleted via subcortical NOP receptors.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
