Chronic Ethanol Potentiates the Effect of Neuropeptide S in the Basolateral Amygdala and Shows Increased Anxiolytic and Anti-Depressive Effects

Enquist, Johan; Ferwerda, Madeline; Madhavan, Anuradha; Hok, Derek; Whistler, Jennifer L.

doi:10.1038/npp.2012.102

Cited by 24 publications

(29 citation statements)

References 43 publications

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“…One swim session was performed per mouse, as described in Enquist et al (). Wild‐type or β‐arrestin 2 KO C57BL/6 mice aged 6–7 weeks ( n = 10–13) were injected with SNC80 (20 mg⋅kg −1 , s.c.) or TAN‐67 (25 mg⋅kg −1 s.c. in saline) 30 min before the test.…”

Section: Methodsmentioning

confidence: 99%

β‐Arrestin 2 dependence of δ opioid receptor agonists is correlated with alcohol intake

Chiang

Sansuk

Rijn

2015

British J Pharmacology

106

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BACKGROUND AND PURPOSEδ Opioid receptor agonists are being developed as potential treatments for depression and alcohol use disorders. This is particularly interesting as depression is frequently co-morbid with alcohol use disorders. Yet we have previously shown that δ receptor agonists range widely in their ability to modulate alcohol intake; certain δ receptor agonists actually increase alcohol consumption in mice. We propose that variations in β-arrestin 2 recruitment contribute to the differential behavioural profile of δ receptor agonists. EXPERIMENTAL APPROACHWe used three diarylmethylpiperazine-based non-peptidic δ receptor selective agonists (SNC80, SNC162 and ARM390) and three structurally diverse δ receptor agonists (TAN-67, KNT127 and NIH11082). We tested these agonists in cAMP and β-arrestin 2 recruitment assays and a behavioural assay of alcohol intake in male C57BL/6 mice. We used β-arrestin 2 knockout mice and a model of depression-like behaviour to further study the role of β-arrestin 2 in δ receptor pharmacology. KEY RESULTSAll six tested δ receptor agonists were full agonists in the cAMP assay but displayed distinct β-arrestin 2 recruitment efficacy. The efficacy of δ receptor agonists to recruit β-arrestin 2 positively correlated with their ability to increase alcohol intake (P < 0.01). The effects of the very efficacious recruiter SNC80 on alcohol intake, alcohol place preference and depression-like behaviour were β-arrestin 2-dependent. CONCLUSIONS AND IMPLICATIONSOur finding that δ receptor agonists that strongly recruit β-arrestin 2 can increase alcohol intake carries important ramifications for drug development of δ receptor agonists for treatment of alcohol use disorders and depressive disorders.

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Section: Methodsmentioning

confidence: 99%

β‐Arrestin 2 dependence of δ opioid receptor agonists is correlated with alcohol intake

Chiang

Sansuk

Rijn

2015

British J Pharmacology

106

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“…Other relevant neurotransmitters involved in stress reactivity and alcohol consumption are norepinephrine, opioids, cholecystokinin, corticotrophin-releasing factors, and neuropeptide Y (Brady and Sinha 2005); impairments of the benzodiazepine receptor are probably also involved. More recently, the role of neuropeptide S in the basolateral amygdala and the relevance of neuropeptide S for the anxiolytic effects of alcohol have been stressed (Enquist et al 2012). Recently, the role of corticotrophin-releasing hormone-2 receptor gene variants for HPA activation and alcohol consumption in the animal model was demonstrated (Yong et al 2014).…”

Section: Definition Of Anxiety Disordersmentioning

confidence: 99%

Comorbidity of Anxiety Disorders and Substance Use

Soyka

2014

Co-Occurring Addictive and Psychiatric Disorders

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“…; Enquist et al . ). This is not surprising as low NPS‐ergic activity is associated with anxiety, whereas high NPS‐ergic activity is linked to arousal, hyperlocomotion/impulsivity (e.g.…”

Section: Introductionmentioning

confidence: 97%

Neuropeptide S receptor gene variant and environment: contribution to alcohol use disorders and alcohol consumption

et al. 2014

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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.

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Chronic Ethanol Potentiates the Effect of Neuropeptide S in the Basolateral Amygdala and Shows Increased Anxiolytic and Anti-Depressive Effects

Cited by 24 publications

References 43 publications

β‐Arrestin 2 dependence of δ opioid receptor agonists is correlated with alcohol intake

β‐Arrestin 2 dependence of δ opioid receptor agonists is correlated with alcohol intake

Comorbidity of Anxiety Disorders and Substance Use

Neuropeptide S receptor gene variant and environment: contribution to alcohol use disorders and alcohol consumption

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