Intraventricular administration of neuropeptide S has reward-like effects.
TL;DR: The data suggest that intraventricular NPS injections have reward-like effects in that NPS weakly facilitates seeking and induces positive reinforcement, which may depend on intact dopamine and hypocretin systems.
About: This article is published in European Journal of Pharmacology.The article was published on 2011-05-01 and is currently open access. It has received 23 citations till now. The article focuses on the topics: Neuropeptide S & SCH-23390.
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TL;DR: The present findings suggest that the analgesic effects of NPS are linked with dopaminergic neurotransmission mainly through dopamine D2-like receptor signaling.
8 citations
TL;DR: A growing body of evidence suggests a close relationship between neuropeptide S and its receptor (NPSR) system in PD: double immunofluorescence labeling studies showed that NPSR is expressed in the nigral tyrosine hydroxylase (TH)-positive neurons; central administration of NPS increases spontaneous locomotion in naive rodents, and central administration is able to ameliorate motor and nonmotor dysfunctions in animal models of PD.
Abstract: Parkinson disease (PD) is a neurodegenerative disease mainly characterized by the loss of nigral dopaminergic neurons in the substantia nigra pars compacta. Patients suffering from PD develop severe motor dysfunctions and a myriad of non-motor symptoms. The treatment mainly consists of increasing central dopaminergic neurotransmission and alleviating motor symptoms, thus promoting severe side effects without modifying the disease's progress. A growing body of evidence suggests a close relationship between neuropeptide S (NPS) and its receptor (NPSR) system in PD: (i) double immunofluorescence labeling studies showed that NPSR is expressed in the nigral tyrosine hydroxylase (TH)-positive neurons; (ii) central administration of NPS increases spontaneous locomotion in naive rodents; (iii) central administration of NPS ameliorates motor and nonmotor dysfunctions in animal models of PD; (iv) microdialysis studies showed that NPS stimulates dopamine release in naive and parkinsonian rodents; (v) central injection of NPS decreases oxidative damage to proteins and lipids in the rodent brain; and, (vi) 7 days of central administration of NPS protects from the progressive loss of nigral TH-positive cells in parkinsonian rats. Taken together, the NPS/NPSR system seems to be an emerging therapeutic strategy for alleviating motor and non-motor dysfunctions of PD and, possibly, for slowing disease progress.
3 citations
TL;DR: This chapter provides an overview of the literature in relation to the roles of NPS and MC4 in drug-seeking behaviors and then provides a medicinal chemistry-based survey of the small molecule ligands for each receptor.
Abstract: There is a vital need for novel approaches and biological targets for drug discovery and development. Treatment strategies for substance use disorders (SUDs) to date have been mostly ineffective other than substitution-like therapeutics. Two such targets are the peptide G-protein-coupled receptors neuropeptide S (NPS) and melanocortin 4 (MC4). Preclinical evidence suggests that antagonists, inverse agonists, or negative allosteric modulators of these receptors might be novel therapeutics for SUDs. NPS is a relatively unexplored receptor with high potential for treating SUD. MC4 has a strong link to early-onset obesity, and emerging evidence suggests significant overlap between food-maintained and drug-maintained behaviors making MC4 an intriguing target for SUD. This chapter provides an overview of the literature in relation to the roles of NPS and MC4 in drug-seeking behaviors and then provides a medicinal chemistry-based survey of the small molecule ligands for each receptor.
2 citations
References
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TL;DR: It is found that the dopamine neurons of sensitized animals have become increasingly sensitive to excitatory pharmacological and environmental stimuli or desensitized to inhibitory regulation, and changes in cellular activity or protein synthesis may result in a change in the presynaptic regulation of axon terminal dopamine release.
2,042 citations
"Intraventricular administration of ..." refers background in this paper
..., 2005), while behavioral sensitization depends on their actions in the ventral tegmental area (Kalivas and Stewart, 1991; Kalivas and Weber, 1988; Vezina and Stewart, 1990)....
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TL;DR: Experiments suggest that dopaminergic neurons localized in the posteromedial ventral tegmental area (VTA) and central linear nucleus raphe selectively project to the ventromedial striatum (medial olfactory tubercle and medial nucleus accumbens shell), whereas the anteromedial VTA has few if any projections to the vents of the ventral striatum.
1,387 citations
"Intraventricular administration of ..." refers background in this paper
...Because dopamine transmission occurring in the medial part of the ventral striatum plays a critical role in reward seeking (Ikemoto, 2007; Shin et al., 2010), the medial ventral striatum may play a critical role in cue-assisted self-administration of NPS....
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TL;DR: It is reported that a neuropeptide, NPS, potently modulates wakefulness and could also regulate anxiety, and it is shown that the LC region encompasses distinct nuclei expressing different arousal-promoting neurotransmitters.
474 citations
"Intraventricular administration of ..." refers background in this paper
...In addition, the fact that intraventricular NPS promotes locomotor activity and wakefulness (Xu et al., 2004) makes it unclear whether increased lever pressing was due to enhanced seeking or “general” arousal....
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...Neuropeptide S (NPS) is a recently identified endogenous ligand of an orphan G protein coupled receptor (Xu et al., 2004)....
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TL;DR: Over a short period in the late 1990s, three groups converged on the discovery of a neuropeptide system, centred in the dorsolateral hypothalamus, that regulates arousal states, influences feeding and is implicated in the sleep disorder narcolepsy.
Abstract: Over a short period in the late 1990s, three groups converged on the discovery of a neuropeptide system, centred in the dorsolateral hypothalamus, that regulates arousal states, influences feeding and is implicated in the sleep disorder narcolepsy. Subsequent studies have illuminated many aspects of the circuitry of the hypocretin (also called orexin) system, which also influences hormone secretion and autonomic homeostasis, and have led to the hypothesis that most human narcolepsies result from an autoimmune attack against the hypocretin-producing neurons. The biochemical, physiological and anatomical components that regulate the switch between waking and sleeping are becoming clear. The rapidity with which the hypocretin story has emerged is a testament to both the conceptual and the technical evolution of genomic science in the past two decades.
426 citations
TL;DR: A neurobiological theory claiming that there is an intrinsic central process that coordinates various selective functions (including perceptual, visceral, and reinforcement processes) into a global function of approach is outlined.
391 citations
"Intraventricular administration of ..." refers background in this paper
...…to be expressed throughout the brain (Leonard and Ring, 2011; Xu et al., 2007), including in the regions that are associated with reward processes (Ikemoto, 2010): the ventral tegmental area, olfactory tubercle, bed nucleus of stria terminalis, diagonal band, paraventricular thalamic nucleus,…...
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..., 2007), including in the regions that are associated with reward processes (Ikemoto, 2010): the ventral tegmental area, olfactory tubercle, bed nucleus of stria terminalis, diagonal band, paraventricular thalamic nucleus, preoptic area, lateral and posterior hypothalamic areas, periaqueductal gray, median and dorsal raphe nuclei and parabrachial nucleus....
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