Blockade of NOP receptor modulates anxiety-related behaviors in mice exposed to inescapable stress

Silva, Aldemara I.; Holanda, Victor A.D.; Neto, Joaquim Azevedo; Silva, Edilson D; Soares-Rachetti, Vanessa P.; Calò, Girolamo; Ruzza, Chiara; Gavioli, Elaine C.

doi:10.1007/s00213-020-05487-y

Cited by 12 publications

(10 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recent evidence showed that also NOP antagonists are effective in reducing alcohol drinking [65,66]. Whereas blockade of the NOP receptor attenuates anxiety-like responses associated with stress or to depressive-like condition [67].…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of Nociceptin/Orphanin FQ and Dynorphin Systems in the Extended Amygdala of Alcohol Preferring Marchigian Sardinian (msP) Rats

Caputi

Stopponi

Rullo

et al. 2021

IJMS

View full text Add to dashboard Cite

Previous studies have shown that genetically selected Marchigian Sardinian alcohol-preferring (msP) rats consume excessive amounts of ethanol to self-medicate from negative moods and to relieve innate hypersensitivity to stress. This phenotype resembling a subset of alcohol use disorder (AUD) patients, appears to be linked to a dysregulation of the equilibrium between stress and antistress mechanisms in the extended amygdala. Here, comparing water and alcohol exposed msP and Wistar rats we evaluate the transcript expression of the anti-stress opioid-like peptide nociceptin/orphanin FQ (N/OFQ) and its receptor NOP as well as of dynorphin (DYN) and its cognate κ-opioid receptor (KOP). In addition, we measured the transcript levels of corticotropin-releasing factor (CRF), CRF receptor 1 (CRF1R), brain-derived neurotrophic factor (BDNF) and of the tropomyosin receptor kinase B receptor (Trk-B). Results showed an innately up-regulation of the CRFergic system, mediating negative mood and stress responses, as well as an inherent up-regulation of the anti-stress N/OFQ system, both in the amygdala (AMY) and bed nucleus of the stria terminalis (BNST) of msP rats. The up-regulation of this latter system may reflect an attempt to buffer the negative condition elicited by the hyperactivity of pro-stress mechanisms since results showed that voluntary alcohol consumption dampened N/OFQ. Alcohol exposure also reduced the expression of dynorphin and CRF transmissions in the AMY of msP rats. In the BNST, alcohol intake led to a more complex reorganization of these systems increasing receptor transcripts in msP rats, along with an increase of CRF and a decrease of N/OFQ transcripts, respectively. Moreover, mimicking the effects of alcohol in the AMY we observed that the activation of NOP receptor by intracerebroventricular administration of N/OFQ in msP rats caused an increase of BDNF and a decrease of CRF transcripts. Our study indicates that both stress and anti-stress mechanisms are dysregulated in the extended AMY of msP rats. The voluntary alcohol drinking, as well as NOP agonism, have a significant impact on neuropeptidergic systems arrangement, bringing the systems back to normalization.

show abstract

Section: Discussionmentioning

confidence: 99%

Dysregulation of Nociceptin/Orphanin FQ and Dynorphin Systems in the Extended Amygdala of Alcohol Preferring Marchigian Sardinian (msP) Rats

Caputi

Stopponi

Rullo

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Установлено, что активация NOP рецепторов агонистами может способствовать развитию депрессивно-подобных состояний у стрессированных грызунов, тогда как антагонисты обладают анксиолитическим действием [70,71]. Вместе с тем, подобный эффект антагонистов NOPr проявлялся только у особей с высокой склонностью к депрессивно-подобному поведению ("helpless") [72], тогда как у стресс-устойчивых ("non-helpless") животных отмечался обратный -анксиогенный эффект [72]. Интересно, что у интактных, то есть не стрессированных животных, изменений в поведении при введении антагониста NOPr не наблюдалось [72].…”

Section: тревожность: анксиолитический или анксиогенный эффекты стимуunclassified

“…Вместе с тем, подобный эффект антагонистов NOPr проявлялся только у особей с высокой склонностью к депрессивно-подобному поведению ("helpless") [72], тогда как у стресс-устойчивых ("non-helpless") животных отмечался обратный -анксиогенный эффект [72]. Интересно, что у интактных, то есть не стрессированных животных, изменений в поведении при введении антагониста NOPr не наблюдалось [72]. В тесте "представление хищника" у мышей антагонисты NOPr могут оказывать как анксиолитическое, так и антидепрессивное действие, не затрагивая иные формы поведения [73].…”

Section: тревожность: анксиолитический или анксиогенный эффекты стимуunclassified

“…При этом антагонист NOPr SB-612111 оказывает анксиолитическое действие у мышей в стадии истощения ответа на стресс, но не у интактных животных. В то же время эффект сменяется на противоположный у мышей в стадии резистентности [72].…”

Section: тревожность: анксиолитический или анксиогенный эффекты стимуunclassified

See 1 more Smart Citation

The role of nociceptin in opioid regulation of brain functions

et al. 2021

View full text Add to dashboard Cite

This review discusses our current knowledge on the nociceptin/orphanin (N/OFQ) system regarding its role in regulation of brain functions. Nociceptin receptor (NOPr) was identified in 1994 [Bunzow et al., 1994; Mollereau et al., 1994]. In 1995 a 17 amino acid endogenous peptide was found to be the high-affinity ligand for the NOPr [Reinscheid et al., 1995]. N/OFQ has a broad spectrum of activity and can act as on opioid-like as well as an anti-opioid peptide. Considering high level of N/OFQ and NOPr mRNA expression in the limbic brain regions, the N/OFQ/NOP system is suggested to be involved in regulation of emotions, resward, pain sensitivity, stress responsibility, sexual behavior, aggression, drug abuse and addiction. However it is still not well understood whether an increased vulnerability to drugs of abuse may be associated with dysregulation of N/OFQ/NOP system. Current review further highlights a need for further research on N/OFQ/NOP system as it could have clinical utility for substance abuse, depression, and anxiety pharmacotherapy.

show abstract

“…The electric footshock as a stress stimulus was used to induce anxiety-like behaviors in mice. It is known that many studies effectively produce an adequate anxiety-like state and fear response through inescapable electric foot shock exposure (Silva et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

The Effect of Serotonin-Norepinephrine Reuptake Inhibitor Milnacipran on Anxiety-like Behaviors in Diabetic Mice

Ulya

Ardianto

Rahmadi

et al. 2021

JFIKI

View full text Add to dashboard Cite

Background: Diabetes mellitus is a chronic disease that causes neuronal plasticity and increased hypothalamic pituitary adrenal (HPA) axis of stress disorders. The change in metabolism is reportedly associated with inadequate response to antianxiety and antidepressant agents. Objective: This study aimed to determine the effect of milnacipran antidepressants on anxiety-like behavior in mice with diabetes mellitus. Methods: Male ICR mice were divided into naive, stress, diabetes mellitus (DM), DM + stress groups to measure anxiety-like behavior. Diabetes mellitus was induced using alloxan, and electric footshock stress was used as a stressor for 14 consecutive days. Anxiety-like behavior was measured using the light-dark box (LDB) and elevated plus maze (EPM) test at days 0, 7 and 14. The antidepressant milnacipran (MIL) was given for 7 days, on days 8 to 14. On day 14, evaluation of anxiety-like behavior after administration of MIL was carried out in all groups using LDB and EPM tests. Results: The results showed that administration of milnacipran effectively ameliorated anxiety-like behavior in the non-DM, but not in the DM group, using the LDB test. A similar result was demonstrated in the EPM test showing the non-DM group's attenuation after milnacipran administration. Conclusion: The present results indicate that there is an inadequate attenuation of the anxiety-like behavior after treatment with milnacipran in diabetes conditions.

show abstract

Blockade of NOP receptor modulates anxiety-related behaviors in mice exposed to inescapable stress

Cited by 12 publications

References 79 publications

Dysregulation of Nociceptin/Orphanin FQ and Dynorphin Systems in the Extended Amygdala of Alcohol Preferring Marchigian Sardinian (msP) Rats

Dysregulation of Nociceptin/Orphanin FQ and Dynorphin Systems in the Extended Amygdala of Alcohol Preferring Marchigian Sardinian (msP) Rats

The role of nociceptin in opioid regulation of brain functions

The Effect of Serotonin-Norepinephrine Reuptake Inhibitor Milnacipran on Anxiety-like Behaviors in Diabetic Mice

Contact Info

Product

Resources

About