Decreased gene expression of neuropeptide Y and its receptors in hippocampal regions during ethanol withdrawal in rats

Olling, Janne Damm; Ulrichsen, Jakob; Haugbøl, Steven; Glenthøj, Birte; Hemmingsen, Ralf

doi:10.1016/j.neulet.2007.07.050

Cited by 16 publications

(38 citation statements)

References 23 publications

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“…NPY protein and mRNA is decreased during withdrawal (Bison & Crews, 2003;Olling et al, 2007;Roy & Pandey, 2002;Walker et al, 2010), which is consistent with studies demonstrating increased ethanol consumption following blockade of NPY signaling (Thiele et al, 1998;Thiele et al, 2000;Thiele, Harding, Juzytsch, Fletcher, & Shaham, 2002). Intracranial infusion or viral overexpression of NPY can also reduce signs of ethanol withdrawal (Woldbye, Ulrichsen, Haugbøl, & Bolwig, 2002) and reduce abstinence-induced intake (Gilpin, Stewart, Murphy, Li, & Badia-Elder, 2003;Thorsell et al, 2007).…”

Section: Relationship Between Withdrawal and Alcohol Consumptionsupporting

confidence: 86%

The Effects of Stress on Measures of Alcohol Drinking in Rodents

Radke

Pickens

Holmes

2014

Neurobiology of Alcohol Dependence

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Section: Relationship Between Withdrawal and Alcohol Consumptionsupporting

confidence: 86%

The Effects of Stress on Measures of Alcohol Drinking in Rodents

Radke

Pickens

Holmes

2014

Neurobiology of Alcohol Dependence

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“…In the EPM, an anxiolytic effect in naïve animals has been observed following treatment with another NPY-Y2 receptor antagonist BIIE0246 (326) but the finding could not be repeated here. Decreased protein and gene expression of NPY and its receptors has been observed in the rat brain during alcohol withdrawal in rats (196,327), strengthening the idea that the NPY system is recruited during alcohol withdrawal. …”

Section: Cym-9840 Prevented Acute Alcohol-induced Withdrawal Anxietymentioning

confidence: 68%

“…Low expression of NPY in the amygdala promotes high levels of alcohol drinking while high levels of NPY in the hippocampus may play a protective role against excessive alcohol consumption (195). The hippocampal NPY system is downregulated during alcohol withdrawal and these neuroadaptive changes could play a role in mediating withdrawal hyperexcitability (196). ICV administration of NPY significantly reduces withdrawal symptoms in rats.…”

Section: Neuropeptide Y In the Modulation Of Food And Alcoholintakementioning

confidence: 99%

Neuropeptide Receptors as Treatment Targets in Alcohol Use Disorders

Aziz¹

2017

Linköping University Medical Dissertations

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Alcohol use disorder (AUD) is a complex disorder with multiple pathophysiological processes contributing to the initiation, progression and development of the disease state. AUD is a chronic relapsing disease with escalation of alcohol-intake over time in repeated cycles of tolerance, abstinence and relapse and hence, it is very difficult to treat. There are only a few currently available treatments with narrow efficacy and variable patient response. Thus it is important to find new, more effective medications to increase the number of patients who can benefit from pharmacological treatment of AUD.The research presented in this thesis work focuses on the critical involvement of central neuropeptides in alcohol-related behaviors. The overall aim was to evaluate the nociceptin/orphanin FQ (NOP) receptor, the neuropeptide Y (NPY) Y2 receptor and the melanin-concentrating hormone (MCH) receptor 1 as novel and potential pharmacological treatment targets for AUD by testing the NOP receptor agonist SR-8993, the NPY-Y2 receptor antagonist CYM-9840 and the MCH1 receptor antagonist GW803430 in established animal models.In the first study (Paper I), the novel and selective NOP agonist SR-8993 was assessed in rat models of motivation to obtain alcohol and relapse to alcohol-seeking behavior using the operant self-administration (SA) paradigm. Firstly, treatment with SR-8993 (1 mg/kg) showed a mildly anxiolytic effect and reversed acute alcohol withdrawal-induced "hangover" anxiety in the elevated plus-maze (EPM). Next, it potently attenuated alcohol SA and motivation to obtain alcohol in the progressive ratio responding (PRR) and reduced both alcohol cue-induced and yohimbine stressinduced reinstatement of alcohol seeking, without affecting the pharmacology and metabolism of alcohol nor other control behaviors. To extend these findings, SR-8993 was evaluated in escalated alcohol-intake in rats. Treatment with SR-8993 significantly suppressed alcohol-intake and preference in rats that were trained to consume high amounts of alcohol in the two-bottle free choice intermittent access (IA) paradigm. SR-8993 also blocked operant SA of alcohol in rats that showed robust escalation in operant alcohol SA following chronic IA exposure to alcohol.In the second study (Paper II), SR-8993 was further evaluated in a model for escalated alcohol-intake induced by long-term IA exposure to alcohol. The effect of previous experience on operant alcohol SA on two-bottle free choice preference drinking was evaluated and sensitivity to treatment with SR-8993 was tested in rats selected for escalated and non-escalated alcohol seeking behavior. We found that rats exposed to the combined SA-IA paradigm showed greater sensitivity to SR-8993 treatment. In addition, acute escalation of alcohol SA after a three-week period of abstinence was completely abolished by pretreatment with SR-8993.In the third study (Paper III), the effects of the novel, small molecule NPY-Y2 antagonist CYM-9840 were tested in operant alcohol SA, PRR which is a model for...

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“…For instance, NPY levels in various brain regions are profoundly affected by chronic administration of cocaine (Wahlestedt et al, 1991) and alcohol (Olling et al, 2007). In P rats, intracerebroventricular (ICV) administration of NPY suppressed voluntary alcohol consumption (Badia-Elder et al, 2001; Thiele and Badia-Elder, 2003; Thorsell et al, 2005a, b; Gilpin et al, 2008c) and over-expression of Npy in the amygdala suppressed increased alcohol intake of animals after repeated alcohol deprivation (Thorsell et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Npy deletion in an alcohol non-preferring rat model elicits differential effects on alcohol consumption and body weight

Qiu

Bell

Cao

et al. 2016

Journal of Genetics and Genomics

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Neuropeptide Y (NPY) is widely expressed in the central nervous system and influences many physiological processes. It is located within the rat quantitative trait locus (QTL) for alcohol preference on chromosome 4. Alcohol-nonpreferring (NP) rats consume very little alcohol, but have significantly higher NPY expression in the brain than alcohol-preferring (P) rats. We capitalized on this phenotypic difference by creating an Npy knockout (KO) rat using the inbred NP background to evaluate NPY effects on alcohol consumption. Zinc finger nuclease (ZNF) technology was applied, resulting in a 26-bp deletion in the Npy gene. RT-PCR, Western blotting and immunohistochemistry confirmed the absence of Npy mRNA and protein in KO rats. Alcohol consumption was increased in Npy+/− but not Npy−/− rats, while Npy−/− rats displayed significantly lower body weight when compared to Npy+/+ rats. In whole brain tissue, expression levels of Npy-related and other alcohol-associated genes, Npy1r, Npy2r, Npy5r, Agrp, Mc3r, Mc4r, Crh and Crh1r, were significantly greater in Npy−/− rats, whereas Pomc and Crhr2 expressions were highest in Npy+/− rats. These findings suggest that the NPY-system works in close coordination with the melanocortin (MC) and corticotropin-releasing hormone (CRH) systems to modulate alcohol intake and body weight.

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Decreased gene expression of neuropeptide Y and its receptors in hippocampal regions during ethanol withdrawal in rats

Cited by 16 publications

References 23 publications

The Effects of Stress on Measures of Alcohol Drinking in Rodents

The Effects of Stress on Measures of Alcohol Drinking in Rodents

Neuropeptide Receptors as Treatment Targets in Alcohol Use Disorders

Npy deletion in an alcohol non-preferring rat model elicits differential effects on alcohol consumption and body weight

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