Back to Search
Start Over
Blockade of nociceptin/orphanin FQ receptor signaling in rat substantia nigra pars reticulata stimulates nigrostriatal dopaminergic transmission and motor behavior
- Publication Year :
- 2004
- Publisher :
- Imperial College Press, 2004.
-
Abstract
- A multidisciplinary approach was followed to investigate whether the opioid-like peptide nociceptin/orphanin FQ (N/OFQ) regulates the nigrostriatal dopaminergic pathway and motor behavior. Nigrostriatal dopaminergic cells, which express N/OFQ peptide (NOP) receptors, are located in the substantia nigra pars compacta and extend their dendrites in the substantia nigra pars reticulata, thereby modulating the basal ganglia output neurons.In vitroelectrophysiological recordings demonstrated that N/OFQ hyperpolarized the dopaminergic cells of the substantia nigra pars compacta and inhibited their firing activity.In vivodual-probe microdialysis showed that N/OFQ perfused in the substantia nigra pars reticulata reduced dopamine release in the ipsilateral striatum, whereas UFP-101 ([Nphe1,Arg14,Lys15]N/OFQ(1-13)-NH2) (a selective NOP receptor peptide antagonist) stimulated it. N/OFQ microinjected in the substantia nigra pars reticulata impaired rat performance on a rotarod apparatus, whereas UFP-101 enhanced it. Electromyography revealed that N/OFQ and UFP-101 oppositely affected muscle tone, inducing relaxation and contraction of triceps, respectively. The selective NOP receptor nonpeptide antagonist J-113397 (1-[3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H benzimidazol-2-one), either injected intranigrally or given systemically, also elevated striatal dopamine release and facilitated motor activity, confirming that these effects were caused by blockade of endogenous N/OFQ signaling. The inhibitory role played by endogenous N/OFQ on motor activity was additionally strengthened by the finding that mice lacking the NOP receptor gene outperformed wild-type mice on the rotarod. We conclude that NOP receptors in the substantia nigra pars reticulata, activated by endogenous N/OFQ, drive a physiologically inhibitory control on motor behavior, possibly via modulation of the nigrostriatal dopaminergic pathway.
- Subjects :
- Male
medicine.medical_specialty
Microinjections
Dopamine
Narcotic Antagonists
Microdialysis
NOP
Substantia nigra
Behavioral/Systems/Cognitive
Striatum
Nociceptin/orphanin FQ
Motor activity
Nociceptin Receptor
Rats, Sprague-Dawley
Mice
Piperidines
Dopamine release
Internal medicine
Basal ganglia
medicine
Animals
J-113397
N/OFQ
UFP-101
Mice, Knockout
Pars compacta
Chemistry
General Neuroscience
Dopaminergic
Corpus Striatum
Rats
Mice, Inbred C57BL
Nociceptin receptor
Endocrinology
Opioid Peptides
nervous system
Muscle Tonus
Receptors, Opioid
Benzimidazoles
Neuroscience
Signal Transduction
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....4b413f623c2d73ab3f93227e8e17a497