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: In this article, the authors discuss manipulations aimed at persistently enhancing anxiety-related behavior in the laboratory mouse using phenotypic selection, genetic techniques and/or environmental manipulations.
Abstract: Mice are increasingly overtaking the rat model organism in important aspects of anxiety research, including drug development. However, translating the results obtained in mouse studies into information that can be applied in clinics remains challenging. One reason may be that most of the studies so far have used animals displaying 'normal' anxiety rather than 'psychopathological' animal models with abnormal (elevated) anxiety, which more closely reflect core features and sensitivities to therapeutic interventions of human anxiety disorders, and which would, thus, narrow the translational gap. Here, we discuss manipulations aimed at persistently enhancing anxiety-related behavior in the laboratory mouse using phenotypic selection, genetic techniques and/or environmental manipulations. It is hoped that such models with enhanced construct validity will provide improved ways of studying the neurobiology and treatment of pathological anxiety. Examples of findings from mouse models of enhanced anxiety-related behavior will be discussed, as well as their relation to findings in anxiety disorder patients regarding neuroanatomy, neurobiology, genetic involvement and epigenetic modifications. Finally, we highlight novel targets for potential anxiolytic pharmacotherapeutics that have been established with the help of research involving mice. Since the use of psychopathological mouse models is only just beginning to increase, it is still unclear as to the extent to which such approaches will enhance the success rate of drug development in translating identified therapeutic targets into clinical trials and, thus, helping to introduce the next anxiolytic class of drugs.
88 citations
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...In addition to its strong influence on stress-induced anxiety-related behavior, the NPS and its NPSR have been shown to be involved in many other physiological and pathological processes including depression-like behavior [306], drug seeking [312], food intake [313], respiratory function [314], asthma/atopy [315-318] and inflammatory bowel disease [319]....
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TL;DR: The results not only enlighten the path of NPS in the brain, but also establish a non-invasive method for NPS administration in mice, thus strongly encouraging translation into a novel therapeutic approach for pathological anxiety in humans.
79 citations
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...NPS is an excellent candidate for this purpose, as, although reward-like effects have been reported by others (Cao et al, 2011), NPS does not act as a GABAA receptor agonist....
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TL;DR: It is suggested that studies using SB-334867 (and any other 2-methylbenzoxazole-containing compound) should be performed with great care to avoid the confounding effects of the rapid hydrolytic decomposition of this susceptible structure.
56 citations
TL;DR: The potential of the NPS system as a treatment target for addiction is analyzed, with particular attention to the interpretation of findings revealing complex neuroanatomical and functional interactions between NPS, CRF, and the Hcrt-1/Ox-A systems.
37 citations
TL;DR: In the general population, the NPSR1 Asn107Ile polymorphism is associated with AUD and alcohol consumption, dependent on sex, environment and age, in line with the impulsivity and personality regulating role of the N PSR1.
Abstract: The functional polymorphism Asn(107) Ile (rs324981, A > T) of the neuropeptide S receptor (NPSR1) gene is involved in the modulation of traits that affect alcohol use. Hence, we have examined whether the NPSR1 A/T polymorphism is associated with alcohol use disorders (AUD) and alcohol use in a population-representative sample. Lifetime AUD were assessed by the MINI psychiatric interview (n = 501) in the older cohort of the longitudinal Estonian Children Personality Behaviour and Health Study at age 25. Alcohol use, environmental adversities and personality were reported by both the younger (original n = 583) and the older cohort (original n = 593) in three study waves. NPSR1 associations with AUD and alcohol use differed by sex. In females, both AUD [odds ratio (OR) = 7.20 (0.94-55.0), P = 0.029] and harmful alcohol use were more prevalent in A-allele carriers. In contrast, in males, AUD was more frequent in T-allele carriers [OR = 2.75 (1.19-6.36), P = 0.017], especially if exposed to adverse environments at age 15 [OR = 10 (1.18-84.51), P = 0.019]. Alcohol use was higher in male T-allele carriers at ages 15 and 18 as well. Similarly to females, however, the risk allele for higher alcohol use for males at age 25 was the A-allele. Many of the effects on alcohol use were explained by genotype effects on measures of personality. In the general population, the NPSR1 Asn(107) Ile polymorphism is associated with AUD and alcohol consumption, dependent on sex, environment and age. The results are in line with the impulsivity and personality regulating role of the NPSR1.
29 citations
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TL;DR: It was found that daily amphetamine injection into the A10 or A9 dopamine region, but not into the dopamine terminal fields, significantly potentiated the motor stimulant effect of peripherally administered amphetamine.
Abstract: The daily administration of indirect dopamine agonists, including amphetamine and cocaine, results in a progressive increase in the behavioral stimulant effect of these drugs. Behavioral augmentation also has been shown with opioids such as morphine, and it is known that a stimulant action on dopaminergic perikarya in the ventromedial mesencephalon is critical to the development of behavioral sensitization to morphine. To determine if amphetamine-induced behavioral sensitization might also involve the mesencephalic dopamine neurons, amphetamine was microinjected daily for 2 days into regions of the rat brain containing dopamine cell bodies (A10 and A9 dopamine regions), or dopamine terminals (nucleus accumbens and striatum), and 6 days later amphetamine was given peripherally. It was found that daily amphetamine injection into the A10 or A9 dopamine region, but not into the dopamine terminal fields, significantly potentiated the motor stimulant effect of peripherally administered amphetamine. The behavioral sensitization produced by intracranial injection of amphetamine was found to be dose-dependent. Intra-A10 injection of amphetamine also was found to potentiate the motor stimulant effect of peripheral cocaine. These data indicate that an action by amphetamine in the A10 and A9 dopamine regions may play a critical role in the development of behavioral sensitization.
344 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: The results suggest that the D1 antagonist may be more effective at blocking mesolimbic dopamine activity, and that selective D1 receptor activation may be an important component of psychostimulant reward.
279 citations
"Intraventricular administration of ..." refers background in this paper
...025 mg/kg dose in rats does not impair motor process (Koob et al., 1987; Hauber, 1996)....
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TL;DR: The results confirm earlier findings indicating that the site of action of amphetamine critical for the development of behavioral sensitization is the VTA and not the NAC and extend them to the case of cross-sensitization to morphine.
266 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: Data suggest that the NPS system may play a key role in modulating a variety of physiological functions, especially arousal, anxiety, learning and memory, and energy balance, as well as regulate energy homeostasis.
Abstract: Neuropeptide S (NPS) and its receptor (NPSR) constitute a novel neuropeptide system that is involved in regulating arousal and anxiety. The NPS precursor mRNA is highly expressed in a previously undescribed group of neurons located between the locus coeruleus (LC) and Barrington's nucleus. We report here that the majority of NPS-expressing neurons in the LC area and the principal sensory trigeminal nucleus are glutamatergic neurons, whereas many NPS-positive neurons in the lateral parabrachial nucleus coexpress corticotropin-releasing factor (CRF). In addition, we describe a comprehensive map of NPSR mRNA expression in the rat brain. High levels of expression are found in areas involved in olfactory processing, including the anterior olfactory nucleus, the endopiriform nucleus, and the piriform cortex. NPSR mRNA is expressed in several regions mediating anxiety responses, including the amygdaloid complex and the paraventricular hypothalamic nucleus. NPSR mRNA is also found in multiple key regions of sleep neurocircuitries, such as the thalamus, the hypothalamus, and the preoptic region. In addition, NPSR mRNA is strongly expressed in major output and input regions of hippocampus, including the parahippocampal regions, the lateral entorhinal cortex, and the retrosplenial agranular cortex. Multiple hypothalamic nuclei, including the dorsomedial and the ventromedial hypothalamic nucleus and the posterior arcuate nucleus, express high levels of NPSR mRNA, indicating that NPS may regulate energy homeostasis. These data suggest that the NPS system may play a key role in modulating a variety of physiological functions, especially arousal, anxiety, learning and memory, and energy balance. J. Comp. Neurol. 500:84–102, 2007. © 2006 Wiley-Liss, Inc.
260 citations
TL;DR: It is reported that cocaine is readily self-administered into the olfactory tubercle, the most ventral portion of the ventral striatum, and plays a critical role in mediating rewarding action of cocaine.
Abstract: Cocaine has multiple actions and multiple sites of action in the brain. Evidence from pharmacological studies indicates that it is the ability of cocaine to block dopamine uptake and elevate extracellular dopamine concentrations, and thus increase dopaminergic receptor activation, that makes cocaine rewarding. Lesion studies have implicated the nucleus accumbens (the dorsal portion of the "ventral striatum") as the probable site of the rewarding action of the drug. However, the drug is only marginally self-administered into this site. We now report that cocaine (60 or 200 mm in 75 nl/infusion) is readily self-administered into the olfactory tubercle, the most ventral portion of the ventral striatum. Cocaine (200 mm) was self-administered marginally into the accumbens shell but not into the core, dorsal striatum, or ventral pallidum. In addition, cocaine injections (200 mm in 300 nl) into the tubercle but not the shell or ventral pallidum induced conditioned place preference. Rewarding effects of cocaine in the tubercle were blocked by coadministration of dopamine D1 or D2 antagonists (1 mm SCH 23390 or 3 mm raclopride) and were not mimicked by injections of the local anesthetic procaine (800 mm). In conclusion, the tubercle plays a critical role in mediating rewarding action of cocaine.
190 citations