Blockade of Nociceptin/Orphanin FQ Receptor Signaling in Rat Substantia Nigra Pars Reticulata Stimulates Nigrostriatal Dopaminergic Transmission and Motor Behavior

Abstract

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.

Differential Involvement of D1 and D2 Dopamine Receptors in L-DOPA-Induced Angiogenic Activity in a Rat Model of Parkinson's Disease

“…Being the output nuclei of the basal ganglia, the EP and the SNr mediate motor stimulant effects of antiparkinsonian drug treatment (Marti et al, 2004;Robertson and Robertson, 1989). In these two structures, there is a high density of D1 receptors on the terminals of 'direct pathway' (striatonigral) axon fibers (Dawson et al, 1988;Savasta et al, 1986a, b), promoting the release of both GABA and dynorphin (reviewed in Cenci and Lindgren, 2007).…”

Nociceptin/Orphanin FQ Modulates Motor Behavior and Primary Motor Cortex Output Through Receptors Located in Substantia Nigra Reticulata

“…injections of N/OFQ or systemic administration of Ro 64-6198 (a synthetic NOP receptor agonist) facilitated spontaneous locomotion at low doses (Florin et al, 1996;Jenck et al, 1997;Higgins et al, 2001;Kuzmin et al, 2004) and inhibited it at higher ones (Reinscheid et al, 1995;Devine et al, 1996;Rizzi et al, 2001;Higgins et al, 2001;Kuzmin et al, 2004). NOP receptor agonists also inhibited exercise-induced locomotion (as in the rotarod test) although in a monophasic way (Jenck et al, 2000;Higgins et al, 2001;Marti et al, 2004a). In contrast, pharmacological blockade (or genetic deletion) of the NOP receptor did not affect spontaneous locomotion but increased exercise-induced motor activity (Marti et al, 2004a).…”

“…NOP receptor agonists also inhibited exercise-induced locomotion (as in the rotarod test) although in a monophasic way (Jenck et al, 2000;Higgins et al, 2001;Marti et al, 2004a). In contrast, pharmacological blockade (or genetic deletion) of the NOP receptor did not affect spontaneous locomotion but increased exercise-induced motor activity (Marti et al, 2004a). Therefore, it has been proposed that endogenous N/ OFQ acts as a physiological constraint of motor function, being its action more relevant under conditions of motor activation rather than at rest (Marti et al, 2004a).…”

“…In contrast, pharmacological blockade (or genetic deletion) of the NOP receptor did not affect spontaneous locomotion but increased exercise-induced motor activity (Marti et al, 2004a). Therefore, it has been proposed that endogenous N/ OFQ acts as a physiological constraint of motor function, being its action more relevant under conditions of motor activation rather than at rest (Marti et al, 2004a). The neurobiological substrate(s) underlying motor actions of exogenous and endogenous N/OFQ have been investigated.…”

“…The neurobiological substrate(s) underlying motor actions of exogenous and endogenous N/OFQ have been investigated. The N/OFQ-induced hypolocomotion has been related to inhibition of mesencephalic mesoaccumbal (Murphy and Maidment, 1999) and/or nigrostriatal (Marti et al, 2004a) DA neurons. Consistently, injections of the NOP receptor antagonist [Nphe 1 Arg 14 ,Lys 15 ]N/OFQ-NH 2 (UFP-101) in substantia nigra reticulata (SNr) elevated rotarod performance and striatal DA release (Marti et al, 2004a).…”