Neuropeptide Y system in accumbens shell mediates ethanol self-administration in posterior ventral tegmental area

Borkar, Chandrashekhar D.; Upadhya, Manoj A.; Shelkar, Gajanan P.; Subhedar, Nishikant K.; Kokare, Dadasaheb M.

doi:10.1111/adb.12254

Cited by 17 publications

(13 citation statements)

References 44 publications

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“…NPY administration into the NAc shell can also enhance morphine reward, whereas administration of the NPY Y1 receptor antagonist BIBP 3226 decreases morphine reward [33]. In a recent study, NPY infusion into the NAc shell was found to increase self-administration of ethanol into the posterior ventral tegmental area in rats [34]. In the present studies the most consistent difference in NPY immunoreactivity between both HDID lines and the HS mice was seen in the NAc shell.…”

Section: Discussionsupporting

confidence: 63%

“…This suggests that sustained higher levels of NPY in these brain regions of HDID mice are not due to an increase in local production/release of NPY, but rather may reflect upstream alterations in NPY transmission. The arcuate nucleus and the CeA are both potential sources of NPY to the NAc shell [34]. The arcuate nucleus has not yet been examined for either NPY immunoreactivity or gene expression in the HDID and HS lines, and this region may be an additional target to consider in the future.…”

Section: Discussionmentioning

confidence: 99%

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Neuropeptide Y response to alcohol is altered in nucleus accumbens of mice selectively bred for drinking to intoxication

Barkley-Levenson

Ryabinin

Crabbe

2016

Behavioural Brain Research

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The High Drinking in the Dark (HDID) mice have been selectively bred for drinking to intoxicating blood alcohol levels and represent a genetic model of risk for binge-like drinking. Presently, little is known about the specific genetic factors that promote excessive intake in these mice. Previous studies have identified neuropeptide Y (NPY) as a potential target for modulating alcohol intake. NPY expression differs in some rodent lines that have been selected for high and low alcohol drinking phenotypes, as well as inbred mouse strains that differ in alcohol preference. Alcohol drinking and alcohol withdrawal also produce differential effects on NPY expression in the brain. Here, we assessed brain NPY protein levels in HDID mice of two replicates of selection and control heterogeneous stock (HS) mice at baseline (water drinking) and after binge-like alcohol drinking to determine whether selection is associated with differences in NPY expression and its sensitivity to alcohol. NPY levels did not differ between HDID and HS mice in any brain region in the water-drinking animals. HS mice showed a reduction in NPY levels in the nucleus accumbens (NAc) – especially in the shell – in ethanol-drinking animals vs. water-drinking controls. However, HDID mice showed a blunted NPY response to alcohol in the NAc core and shell compared to HS mice. These findings suggest that the NPY response to alcohol has been altered by selection for drinking to intoxication in a region-specific manner. Thus, the NPY system may represent a potential target for altering binge-like alcohol drinking in these mice.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Neuropeptide Y response to alcohol is altered in nucleus accumbens of mice selectively bred for drinking to intoxication

Barkley-Levenson

Ryabinin

Crabbe

2016

Behavioural Brain Research

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“…Neuropeptide Y (NPY), the mammalian homolog of NPF, is a widely expressed neuropeptide (34) and is involved in regulating behaviors such as feeding (35) and alcohol consumption (36). In addition, NPY neurons in the central nucleus of the amygdala and the arcuate nucleus of the hypothalamus send projections to the nucleus accumbens (37), and intraaccumbens injections of NPY are able to produce a place preference response in rats (38). Similarly, the fly NPF neurons regulate several reward related behaviors, such as retrieval of appetitive memories (22), and alcohol preference and reward (10).…”

Section: Discussionmentioning

confidence: 99%

Dissection of theDrosophilaneuropeptide F circuit using a high-throughput two-choice assay

Shao

Saver

Chung

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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In their classic experiments, Olds and Milner showed that rats learn to lever press to receive an electric stimulus in specific brain regions. This led to the identification of mammalian reward centers. Our interest in defining the neuronal substrates of reward perception in the fruit fly Drosophila melanogaster prompted us to develop a simpler experimental approach wherein flies could implement behavior that induces self-stimulation of specific neurons in their brains. The high-throughput assay employs optogenetic activation of neurons when the fly occupies a specific area of a behavioral chamber, and the flies' preferential occupation of this area reflects their choosing to experience optogenetic stimulation. Flies in which neuropeptide F (NPF) neurons are activated display preference for the illuminated side of the chamber. We show that optogenetic activation of NPF neuron is rewarding in olfactory conditioning experiments and that the preference for NPF neuron activation is dependent on NPF signaling. Finally, we identify a small subset of NPF-expressing neurons located in the dorsomedial posterior brain that are sufficient to elicit preference in our assay. This assay provides the means for carrying out unbiased screens to map reward neurons in flies.reward circuit | high-throughput two-choice assay | optogenetics | neuropeptide F | Drosophila

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“…A number of studies in rodents have also shown that NPY elicits reward behaviors through its action in the nucleus accumbens (NAc). For example, administration of NPY into the NAc produced conditioned place preference [6,7] and increased ethanol selfadministration [8]. Accordingly, application of NPY has been reported to cause dopamine release in the striatum in both slice preparations and intact animals [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Neuropeptide Y and representation of salience in human nucleus accumbens

Warthen

Sanford

Walker

et al. 2018

Neuropsychopharmacol

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Neuropeptide Y (NPY) produces anxiolytic effects in rodent models, and naturally occurring low NPY expression in humans has been associated with negative emotional phenotypes. Studies in rodent models have also demonstrated that NPY elicits reward behaviors through its action in the nucleus accumbens (NAc), but the impact of NPY on the human NAc is largely unexplored. We recruited 222 healthy young adults of either sex and genetically selected 53 of these subjects at the extremes of NPY expression (Low-NPY and High-NPY) to participate in functional magnetic resonance imaging. Responses of the NAc and surrounding ventral striatum were quantified during a monetary incentive delay task in which stimuli varied by salience (high versus low) and valence (win versus loss). We found that bilateral NAc responses to high-salience versus low-salience stimuli were greater for Low-NPY subjects relative to High-NPY subjects, regardless of stimulus valence. To our knowledge, these results provide the first evidence in humans linking NPY with salience sensitivity of the NAc, raising the possibility that individual differences in NPY expression moderate the risk for disorders of mesoaccumbal function such as addictions and mood disorders. Additionally, we found that head motion was greater among High-NPY subjects, consistent with previous reports linking NPY with hyperactivity. Future studies in animal models are warranted to elucidate the neural mechanisms through which NPY influences NAc function and related behaviors.

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Neuropeptide Y system in accumbens shell mediates ethanol self-administration in posterior ventral tegmental area

Cited by 17 publications

References 44 publications

Neuropeptide Y response to alcohol is altered in nucleus accumbens of mice selectively bred for drinking to intoxication

Neuropeptide Y response to alcohol is altered in nucleus accumbens of mice selectively bred for drinking to intoxication

Dissection of theDrosophilaneuropeptide F circuit using a high-throughput two-choice assay

Neuropeptide Y and representation of salience in human nucleus accumbens

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