Peripheral and Central Administration of a Selective Neuropeptide Y Y1 Receptor Antagonist Suppresses Ethanol Intake by C57BL/6J Mice

Sparta, Dennis R.; Fee, Jon R.; Hayes, Dayna M.; Knapp, Darin J.; MacNeil, Douglas J.; Thiele, Todd E.

doi:10.1097/01.alc.0000139829.67958.1a

Cited by 32 publications

(33 citation statements)

References 73 publications

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“…Mouse studies indicate that Y 1 Rs mediate the suppressive effects of NPY on alcohol drinking (Thiele et al 2002;Sparta et al 2004;Eva et al 2006). Likewise, acute stress and alcohol withdrawal increase amygdalar Y 1 R expression in rodents (Aguilar-Valles et al 2005;Eva et al 2006;Sommer et al 2008).…”

Section: Neuropeptide Y (Npy) and Alcohol-related Behaviormentioning

confidence: 99%

The Central Amygdala and Alcohol: Role of -Aminobutyric Acid, Glutamate, and Neuropeptides

Roberto

Gilpin

Siggins

2012

Cold Spring Harbor Perspectives in Medicine

118

107

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Alcohol dependence is a chronically relapsing disorder characterized by compulsive drug seeking and drug taking, loss of control in limiting intake, and the emergence of a withdrawal syndrome in the absence of the drug. Accumulating evidence suggests an important role for synaptic transmission in the central amygdala (CeA) in mediating alcohol-related behaviors and neuroadaptative mechanisms associated with alcohol dependence. Acute alcohol facilitates g-aminobutyric acid-ergic (GABAergic) transmission in CeA via both pre-and postsynaptic mechanisms, and chronic alcohol increases baseline GABAergic transmission. Acute alcohol inhibits glutamatergic transmission via effects at N-methyl-D-aspartate (NMDA) and AMPA receptors in CeA, whereas chronic alcohol up-regulates N-methyl-D-aspartate receptor (NMDAR)-mediated transmission. Pro-(e.g., corticotropin-releasing factor [CRF]) and anti-stress (e.g., NPY, nociceptin) neuropeptides affect alcohol-and anxiety-related behaviors, and also alter the alcohol-induced effects on CeA neurotransmission. Alcohol dependence produces plasticity in these neuropeptide systems, reflecting a recruitment of those systems during the transition to alcohol dependence.

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Section: Neuropeptide Y (Npy) and Alcohol-related Behaviormentioning

confidence: 99%

The Central Amygdala and Alcohol: Role of -Aminobutyric Acid, Glutamate, and Neuropeptides

Roberto

Gilpin

Siggins

2012

Cold Spring Harbor Perspectives in Medicine

118

107

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“…Among these, Y 1 , Y 2 , and Y 5 receptors are implicated in modulation of alcohol intake [147 ]. Recent studies showed the NPY Y 1 receptor antagonist to suppress alcohol intake in mice [152]. A naturally occurring functional polymorphism of an NPY receptor-like protein gene (npr-1) in Caenorhabditis elegans negatively regulated the development of acute tolerance [153 ].…”

Section: Neuropeptide Y and Neuropeptide Y Receptorsmentioning

confidence: 99%

New findings on the genetic influences on alcohol use and dependence

Higuchi

Matsushita

Kashima

2006

Current Opinion in Psychiatry

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Despite great advances in understanding of genetic vulnerability in alcohol use disorders, only two gene complexes, ADH and ALDH2, have been identified as having defined effects on alcohol use and liability to dependence in humans. New genes associated with increased risks for the disorder will certainly be added to this list in the near future. Neurobiological analyses of the effects of these genes will surely contribute to further understanding of the cause of alcohol dependence and the interindividual differences in risks.

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“…Neuropeptide Y (NPY) is a 36 amino acid neurotransmitter that is distributed widely in the brain and has been shown to be involved in a variety of biological functions, including food intake, seizure activity, cardiovascular homeostasis, integration of emotional behaviour, thermogenesis and circadian rhythms [152,153]. NPY appears to have functions opposite to those of CRF [154].…”

Section: Neuropeptide Y Agonists/antagonistsmentioning

confidence: 99%

“…In particular, the Y 1 receptor appears to play a role in altering alcohol intake as well as some of the intoxicating effects of alcohol [155]. Blockage of NPY 1 receptors with selective Y 1 antagonists BIBP-3226 and (-)-2-[1-(3-chloro-5-isopropyloxycarbonylaminophenyl)ethylamino]-6-[2-(5-ethyl-4-methyl-1,3-tiazol-2-yl)ethyl]-4-morpholinopyridine reduced alcohol consumption as well as motivation to self-administer alcohol in mice and rats [153,156]. The presynaptic Y 2 receptor may also modulate alcohol drinking behaviour.…”

Section: Neuropeptide Y Agonists/antagonistsmentioning

confidence: 99%

Development of medications for alcohol use disorders: recent advances and ongoing challenges

Litten

Fertig

Mattson

et al. 2005

Expert Opinion on Emerging Drugs

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During the past decade, efforts to develop medications for alcoholism have burgeoned. Three agents, disulfiram, naltrexone and acamprosate, are now approved in a large number of countries. Although many patients have benefited from existing medications, their effects are moderate, and some alcoholics fail to respond to them. A host of new agents are currently under active investigation. Critical barriers must be overcome to ensure that future efforts in the development of medications for alcohol use disorders reach full fruition. These challenges include: establishing key targets for drug discovery; validating animal and human screening models; and developing biomarkers to help predict treatment success. In addition, it is important to formulate methodological and statistical strategies to efficiently conduct alcohol pharmacotherapy trials; to specify genetic and phenotypic patient characteristics associated with efficacy and safety for lead compounds; to forge productive alliances among governmental agencies, the pharmaceutical industry and academic researchers to further drug development; and, ultimately and perhaps most difficult, to engage the practitioner community to incorporate medications into the alcohol treatment process.

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Peripheral and Central Administration of a Selective Neuropeptide Y Y1 Receptor Antagonist Suppresses Ethanol Intake by C57BL/6J Mice

Abstract: These data indicate that acute blockade of the NPY Y1 receptor with a systemically bioavailable NPY Y1RA reduces voluntary ethanol consumption by C57BL/6J mice. These results are consistent with observations that hypothalamic infusion of NPY increases ethanol drinking by rats.

Cited by 32 publications

References 73 publications

The Central Amygdala and Alcohol: Role of -Aminobutyric Acid, Glutamate, and Neuropeptides

The Central Amygdala and Alcohol: Role of -Aminobutyric Acid, Glutamate, and Neuropeptides

New findings on the genetic influences on alcohol use and dependence

Development of medications for alcohol use disorders: recent advances and ongoing challenges

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