Endogenous nitric oxide modulates behavioural effects elicited by substance P in rat

doi:10.1016/0014-2999(94)90790-0

European Journal of Pharmacology

Volume 271, Issues 2–3, 27 December 1994, Pages 329-333

https://doi.org/10.1016/0014-2999(94)90790-0 Get rights and content

Abstract

Several studies have shown that the undecapeptide, substance P, alters behaviour following central or peripheral administration in the rat. Here we report that l-arginine administration increases substance P-induced locomotion and changes in food intake in rats. $N^{G} -Nitro- l -arginine$ methyl ester, a specific inhibitor of nitric oxide synthase, reduces substance P-induced effects. These results suggest that endogenous nitric oxide plays a role in the modulation of the catecholaminergic effect of substance P on motor behaviour. They also clarify the mechanism underlying food intake induced by substance P.

References (25)

J.P. Bolam et al.
Substance P-containing terminals in synaptic contact with cholinergic neurons in the neostriatum and basal forebrain: double immunocytochemical study in the rat
Brain Res.
(1986)
M.J. Brownstein et al.
Regional distribution of substance P in the brain of the rat
Brain Res.
(1976)
A. Calignano et al.
Endogenous nitric oxide modulates morphine-induced changes in locomotion and food intake in mice
Eur. J. Pharmacol.
(1993)
P.J. Elliott et al.
Behavioural effects of tachykinins and related peptides
Brain Res.
(1986)
U. Förstermann et al.
Regional distribution of EDRF/NO-synthesizing enzyme(s) in rat brain
Biochem. Biophys. Res. Commun.
(1990)
J. Garthwaite et al.
NMDA receptor activation induces nitric oxide synthesis from arginine in rat brain slices
Eur. J. Pharmacol.
(1989)
L.H. Greenberg et al.
Enzymate regulation of the concentration of cyclic GMP in mouse
Brain Neuropharmacol.
(1978)
M.E. Hall et al.
Effects of substance P and neurokinin A (substance K) on motor behavior: unique effect of substance P attributable to its amino-terminal sequence
Brain Res.
(1987)
A.E. Kelley et al.
Substance P infusion into substantia nigra of the rat: behavioural analysis and involvement of striatal dopamine
Eur. J. Pharmacol.
(1979)
T. Klockgether et al.
Motor actions of exitanting amino acid and their antagonists within rat ventromedial thalamic nucleus
Brain Res.
(1986)

Y. Kubota et al.

Innervation of substance P neurones by catecholaminergic terminals in the neostriatum

Brain Res.

(1986)

A. Ljungdahl et al.

Distribution of substance P-like immunoreactivity in the central nervous system of the rat. II. Light microscopic localization in relation to catecholamines-containing neurons

Neuroscience

(1978)

Cited by (14)

Nitric Oxide Signaling in the Striatum
2016, Handbook of Behavioral Neuroscience
Citation Excerpt :
Disruption of nNOS function also potentiates catalepsy induced via D2-like receptor antagonist administration (Cavas and Navarro, 2002; Del Bel and Guimaraes, 2000). Additionally, locomotion stimulated by substance P (Mancuso et al., 1994), NMDA receptor antagonists (Deutsch et al., 1996), and D1/5 and D2-like receptor agonists (Starr and Starr, 1995) is decreased following systemic administration of NOS inhibitors. The psychomimetic drug phencyclidine has also been reported to modulate locomotor activity in a manner that is sensitive to both NO donors and nNOS inhibitors, although these studies have produced contradictory results (Bujas-Bobanovic et al., 2000; Johansson et al., 1999, 1997; Klamer et al., 2005; Noda et al., 1995, 1996).
Striatal medium-sized spiny neurons contain high levels of soluble guanylyl cyclase (sGC), 3′-5′-cyclic guanosine monophosphate (cGMP)-dependent protein kinase and other components of the cGMP signaling system. Striatal sGC-cGMP signaling is activated by the gaseous neuromodulator nitric oxide (NO). A growing body of literature indicates that under physiological conditions, NO-producing interneurons are potently activated by glutamate and dopamine (DA). The complex nature of the modulatory effects of NO on striatal neurons likely depends on the effector pathways recruited during NO signaling and the relative activity and subtype of neurons under study. Indeed, a review of electrophysiological studies indicates that NO exerts a variety of effects on local circuit neurons and projection neurons involved in regulating basal ganglia output and motor behavior. In addition to summarizing these influences, this chapter discusses the impact of striatal DA depletion on NO signaling and examines the relevance of nitrergic dysregulation for the pathophysiology of Parkinson's disease.
Brain kinin B1 receptor is upregulated by the oxidative stress and its activation leads to stereotypic nociceptive behavior in insulin-resistant rats
2015, Peptides
Citation Excerpt :
While glutamate is recognized as a classical neurotransmitter involved in various cerebral functions, including NMDA-induced grooming behavior [42], SP is known to initiate stereotypic nocifensive behavior [8,15,29,39] and to contribute to the defence reaction in response to stress [8–10]. In the brain, endogenous NO plays a role in the effect of SP on motor behavior [36]. This is keeping with the presence of all components of the kallikrein–kinin system in normal brain and the upregulation of B1R in pathologic brain [4,11,33,37].
Kinin B1 receptor (B1R) is virtually absent under physiological condition, yet it is highly expressed in models of diabetes mellitus. This study aims at determining: (1) whether B1R is induced in the brain of insulin-resistant rat through the oxidative stress; (2) the consequence of B1R activation on stereotypic nocifensive behavior; (3) the role of downstream putative mediators in B1R-induced behavioral activity. Sprague-Dawley rats were fed with 10% d-glucose in their drinking water or tap water (controls) for 4 or 12 weeks, combined either with a standard chow diet or a diet enriched with α-lipoic acid (1 g/kg feed) for 4 weeks. The distribution and density of brain B1R binding sites were assessed by autoradiography. Behavioral activity evoked by i.c.v. injection of the B1R agonist Sar-[D-Phe⁸]-des-Arg⁹-BK (10 μg) was measured before and after i.c.v. treatments with selective antagonists (10 μg) for kinin B1 (R-715, SSR240612), tachykinin NK1 (RP-67580) and glutamate NMDA (DL-AP5) receptors or with the inhibitor of NOS (L-NNA). Results showed significant increases of B1R binding sites in various brain areas of glucose-fed rats that could be prevented by the diet containing α-lipoic acid. The B1R agonist elicited head scratching, grooming, sniffing, rearing, digging, licking, face washing, wet dog shake, teeth chattering and biting in glucose-fed rats, which were absent after treatment with α-lipoic acid or antagonists/inhibitors. Data suggest that kinin B1R is upregulated by the oxidative stress in the brain of insulin-resistant rats and its activation causes stereotypic nocifensive behavior through the release of substance P, glutamate and NO.
Molsidomine, a nitric oxide donor, modulates rotational behavior and monoamine metabolism in 6-OHDA lesioned rats treated chronically with L-DOPA
2013, Neurochemistry International
Citation Excerpt :
A growing body of evidence derived from animal models reveals a compelling role of nitric oxide (NO), a unique gaseous neurotransmitter and neuromodulator with a broad spectrum of activities in the mammalian brain (Guix et al., 2005), in the regulation of motor function. Behavioral studies have demonstrated that acute administration of selective or non-selective neuronal nitric oxide synthase (nNOS) inhibitors to rodents, reduced spontaneous locomotor activity (Stewart et al., 1994; Dzoljic et al., 1997; Sandi et al., 1995) and hyperlocomotion induced by cocaine (Pudiak and Bozarth, 1993; Przegaliński and Filip, 1997), morphine (Calignano et al., 1993), substance P (Mancuso et al., 1994) and amphetamine or methamphetamine (Przegaliński and Filip, 1997; Ohno and Watanabe, 1995; Abekawa et al., 1994). Locomotor activity enhanced by selective dopamine D1 and D2 receptor agonists (Starr and Starr, 1995; Przegaliński and Filip, 1997) and the NMDA receptor antagonist MK-801 (Deutsch et al., 1996) was also decreased by these inhibitors.
Some biochemical and histological studies of Parkinson’s disease patients’ brains and 6-OHDA-lesioned rats suggest that dopaminergic dennervation of the striatum leads to the nitrergic system hypofunction in this structure. Hence, recently the modulation of nitric oxide (NO)– soluble guanylyl cyclase–cyclic GMP signaling is considered to be a new target for the treatment of Parkinson’s disease. The aim of our study was to examine the impact of chronic combined treatment with low doses of the NO donor molsidomine (2 and 4 mg/kg) and L-DOPA (12.5 and 25 mg/kg) on rotational behavior and monoamine metabolism in the striatum (STR) and substantia nigra (SN) of unilaterally 6-OHDA-lesioned rats.
Chronic administration of molsidomine at a dose of 2 mg/kg jointly with 25 mg/kg of L-DOPA significantly decreased the number of contralateral rotations when compared to L-DOPA alone. Other combinations of the examined drug doses were less effective. The tissue DA levels in the ipsilateral STR and SN after the last chronic doses of molsidomine (2 mg/kg) and L-DOPA (12.5 or 25 mg/kg), were significantly higher than after L-DOPA alone. Chronic L-DOPA treatment alone or jointly with a lower dose of molsidomine decreased 5-HT levels and accelerated its catabolism in the examined structures. However, combination of a higher dose of molsidomine with L-DOPA (25 mg/kg) did not reduce 5-HT content while its catabolism was less intensive. The obtained results show that low doses of molsidomine can modulate rotational behavior and tissue DA and 5-HT concentrations in the STR and SN of 6-OHDA-lesioned rats treated chronically with L-DOPA.
Role of nitric oxide in the regulation of motor function. An overview of behavioral, biochemical and histological studies in animal models
2013, Pharmacological Reports
Citation Excerpt :
A growing body of evidence from animals studies indicates that NO is a key modulator of neuronal activity in the dorsal striatum and a critical factor for the regulation of motor function and synaptic plasticity [37, 158]. Behavioral studies carried out on rodents demonstrated that non-selective and selective nNOS inhibitors reduced spontaneous locomotor activity [43, 137, 143] and hyperlocomotion induced by cocaine [122, 123], morphine [19], substance P [100] as well as by amphetamine or metamphetamine [1, 113, 122]. Also locomotor activity stimulated by selective dopamine D1 and D2 receptor agonists [122, 141] and the N-methyl-D-aspartic acid (NMDA) receptor antagonist MK-801 [39] was decreased by these inhibitors.
A compelling body of evidence suggests that nitric oxide (NO), a unique gaseous neurotransmitter and neuromodulator plays a key role in the regulation of motor function. Recently, the interest of researchers concentrates on the NO – soluble guanylyl cyclase (sGC) – cyclicGMP(cGMP) signaling pathway in the striatum as a new target for the treatment of Parkinson's disease (PD). The aim of the study is to review the available literature referring to the role ofNOin the integration of basal ganglia functions. First, attention has been focused on behavioral effects of NO donors and neuronal nitric oxide synthase (nNOS) inhibitors in the modulation of motor behavior. Then, disturbances in the nitrergic neurotransmission in PD and its 6-OHDA animal model have been presented. Moreover, the most current data demonstrating the contribution of both dopamine and glutamate to the regulation of NO biosynthesis in the striatum have been analyzed. Finally, the role of NO in the tonic and phasic dopamine release as well as in the regulation of striatal output pathways also has been discussed.
Nitric Oxide Signaling in the Striatum
2010, Handbook of Behavioral Neuroscience
Citation Excerpt :
Disruption of NOS function also potentiates catalepsy induced via D2-like receptor antagonist administration (Del Bel and Guimaraes, 2000; Cavas and Navarro, 2002). Additionally, locomotion stimulated by substance P (Mancuso et al., 1994), NMDA receptor antagonists (Deutsch et al., 1996), and D1/5 and D2-like receptor agonists (Starr and Starr, 1995) is decreased following systemic administration of NOS inhibitors. Elevations in striatal levels of cAMP and cGMP observed in PDE1B knock-out mice are associated with greater locomotor hyperactivity induced via administration of DA agonists (Reed et al., 2002).
This chapter reviews that nitric oxide (NO) is a gaseous neuromodulator, which is a key player in the regulation of numerous physiological and pathophysiological processes in both the peripheral and central nervous system. NO has been shown to mediate various forms of synaptic plasticity, including short and long-term changes in the efficacy of excitatory and inhibitory synaptic transmission. Three distinct isoforms of the NO-producing enzyme nitric oxide synthase (NOS; neuronal NOS, inducible NOS, endothelial NOS) have also been described. Of these isoforms, type 1 (neuronal, nNOS) has been shown to be ubiquitously distributed throughout the brain in an uneven manner, and is expressed in the nuclei of the basal ganglia in moderate levels. The chapter also discusses that striatal NOS activity has been reported to be depressed in the striatal complex of post-mortem brains of patients with Parkinson's disease (PD) and dopamine (DA)-depleted animals. Most pathophysiological models and metabolic studies of PD predict that the net effect of these alterations is an imbalance in striatal output in which the indirect pathway becomes functionally hyperactive and the direct pathway is slightly hypoactive. It reviews that future studies examining the impact of DA-depletion on the regulation of striatal NOS activity will further increase the understanding of sensorimotor integration within striatal networks involved in normal motor function and pathophysiological states.
Substance P and its transglutaminase-synthesized spermine derivative elicit yawning behavior via nitric oxide in rats
2001, Peptides
Previously, we showed that intranigrostriatal injection of substance P (SP) cause behavioral changes in rats. Those effects, such as locomotion and food intake, resulted related to catecholamines release modulated by nitric oxide [18]. Here we report that intranigrostriatal injection of SP elicited yawning in rats. Moreover, since in previous studies we demonstrated that transglutaminase-synthesized γ-(glutamyl⁵)spermine derivative of SP (Spm-SP) could be a useful tool in differentiating NK₁ receptors [5], [19], [26], we reports the effects of injecting the selective septide-sensitive NK₁ receptor agonist Spm-SP into the nigrostriatal region of the rat brain on yawning. The administration of L-N^ω-nitroarginine methyl ester, a NO-synthase inhibitor, stereospecifically reduced in a dose related manner both SP and Spm-SP-induced yawning. In contrast, L-arginine pretreatment prevented the effect of NO-synthase inhibitor. Moreover, the NK₁ antagonist RP,67580 blocked yawning behavior induced by both SP and Spm-SP, whereas the pretreatment with systemic reserpine determined its increase. The administration of NO-synthase inhibitor resulted ineffective in reducing SP and Spm-SP-induced yawns in reserpinized rats. Finally, yawns elicited by SP or Spm-SP were blocked when rats were treated with scopolamine but not with methylscopolamine.
These results indicate that yawning induced in rats by SP injection is dependent upon endogenous dopamine levels in brain nigrostriatal area. Moreover, we demonstrate, by using Spm-SP, that septide-sensitive NK₁ receptor are specifically involved in yawning behavior.

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Endogenous nitric oxide modulates behavioural effects elicited by substance P in rat

Abstract

Brain Res.

Brain Res.

Eur. J. Pharmacol.

Brain Res.

Biochem. Biophys. Res. Commun.

Eur. J. Pharmacol.

Brain Neuropharmacol.

Brain Res.

Eur. J. Pharmacol.

Brain Res.

Brain Res.

Neuroscience