Endogenous kappa-opioid mediation of stress-induced potentiation of ethanol-conditioned place preference and self-administration

Sperling, Robin E.; Gomes, Stacey M.; Sypek, Elizabeth I.; Carey, Amanda N.; McLaughlin, Jay P.

doi:10.1007/s00213-010-1844-5

Cited by 117 publications

(147 citation statements)

References 63 publications

(106 reference statements)

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“…Additionally, KOR antagonism blocks stress-induced facilitation of conditioned place preference for cocaine and alcohol (McLaughlin et al, 2006;Sperling et al, 2010). These data suggest that KOR activation is essential to drive stress-induced reward seeking and that functional upregulation of the KOR signaling increases the reinforcing efficacy of drugs of abuse, potentially through alleviation of a withdrawal-associated negative affective state.…”

Section: Therapeutic Effects Of Kor Blockadementioning

confidence: 82%

“…The KOR system modulates DA in the NAc and is involved in regulating both anxiety-like and drug-seeking behaviors (Sperling et al, 2010;Walker et al, 2012;Berger et al, 2013). Experiments in the current study examined the hypothesis that SI-induced alterations in NAc DA signaling involve an upregulation of the dynorphin/KOR system.…”

Section: Discussionmentioning

confidence: 97%

“…These data are consistent with previous studies demonstrating adolescent SI-induced escalations in ethanol intake (McCool and Chappell, 2009;Chappell et al, 2013;Skelly et al, 2015) and cocaine self-administration (Baarendse et al, 2014) in adulthood. Other stressors, such as footshock and forced swim stress, also potentiate cocaine seeking (Buffalari and See, 2009) and ethanol consumption (Sperling et al, 2010), respectively. Furthermore, repeated cycles of intermittent ethanol vapor exposure and withdrawal leads to increases in anxiety during withdrawal and an associated escalation in ethanol intake in adult mice (Griffin et al, 2009;Becker, 2012).…”

Section: Si-induced Potentiation Of Kor System Responsivenessmentioning

confidence: 99%

“…Both repeated forced swim stress and pharmacological activation of KORs with U50,488 increases ethanol consumption in mice (Sperling et al, 2010;Rose et al, 2015). CIE exposure and withdrawal lead to increases in anxiety-like and anhedonic behaviors in addition to promoting an escalation in ethanol intake (Berger et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Early-Life Social Isolation Stress Increases Kappa Opioid Receptor Responsiveness and Downregulates the Dopamine System

Karkhanis¹,

Rose

Weiner³

et al. 2016

Neuropsychopharmacol

113

107

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Chronic early-life stress increases vulnerability to alcoholism and anxiety disorders during adulthood. Similarly, rats reared in social isolation (SI) during adolescence exhibit augmented ethanol intake and anxiety-like behaviors compared with group housed (GH) rats. Prior studies suggest that disruption of dopamine (DA) signaling contributes to SI-associated behaviors, although the mechanisms underlying these alterations are not fully understood. Kappa opioid receptors (KORs) have an important role in regulating mesolimbic DA signaling, and other kinds of stressors have been shown to augment KOR function. Therefore, we tested the hypothesis that SI-induced increases in KOR function contribute to the dysregulation of NAc DA and the escalation in ethanol intake associated with SI. Our ex vivo voltammetry experiments showed that the inhibitory effects of the kappa agonist U50,488 on DA release were significantly enhanced in the NAc core and shell of SI rats. Dynorphin levels in NAc tissue were observed to be lower in SI rats. Microdialysis in freely moving rats revealed that SI was also associated with reduced baseline DA levels, and pretreatment with the KOR antagonist nor-binaltorphimine (nor-BNI) increased DA levels selectively in SI subjects. Acute ethanol elevated DA in SI and GH rats and nor-BNI pretreatment augmented this effect in SI subjects, while having no effect on ethanol-stimulated DA release in GH rats. Together, these data suggest that KORs may have increased responsiveness following SI, which could lead to hypodopaminergia and contribute to an increased drive to consume ethanol. Indeed, SI rats exhibited greater ethanol intake and preference and KOR blockade selectively attenuated ethanol intake in SI rats. Collectively, the findings that nor-BNI reversed SI-mediated hypodopaminergic state and escalated ethanol intake suggest that KOR antagonists may represent a promising therapeutic strategy for the treatment of alcohol use disorders, particularly in cases linked to chronic early-life stress.

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Section: Therapeutic Effects Of Kor Blockadementioning

confidence: 82%

Section: Discussionmentioning

confidence: 97%

Section: Si-induced Potentiation Of Kor System Responsivenessmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Early-Life Social Isolation Stress Increases Kappa Opioid Receptor Responsiveness and Downregulates the Dopamine System

Karkhanis¹,

Rose

Weiner³

et al. 2016

Neuropsychopharmacol

113

107

View full text Add to dashboard Cite

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“…Así mismo, se ha demostrado que el estrés incrementa la ingesta voluntaria de etanol (i.e., Vengeliene et al, 2003), aunque existen resultados contradictorios dependiendo del modelo de estrés empleado, o de determinados parámetros experimentales dentro de un modelo concreto, así como del procedimiento de consumo de etanol utilizado (ver Shina, 2005;Zimmermann, Blomeyer, Laucht, y Mann, 2007; para revisión sobre el tema). Por otra parte, se ha observado que el estrés facilita el CPL (revisado en Lu et al, 2003;Sperling, Gomes, Sypek, Carey y McLaughlin, 2010) y minimiza el CAL inducido por 1.0 g/kg de etanol (Funk, Vohra y Le, 2004).…”

Section: Relación Entre Estrés Y Efectos Motivacionales Del Alcoholunclassified

Una revisión de la literatura experimental sobre los efectos motivacionales del alcohol y su modulación por factores biológicos y ambientales.

2013

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Resumen: El alcohol es posiblemente la droga psicoactiva más consumida en el mundo. La ingesta moderada es común, pero para algunos individuos el consumo de alcohol se convierte en un trastorno adictivo. La progresión desde un consumo moderado de alcohol hasta el abuso podría deberse a la existencia de una sensibilidad diferencial, genéticamente determinada, a los efectos reforzantes y aversivos del alcohol. Así mismo, se sugiere que factores ambientales, como el estrés, podrían intervenir en el inicio del alcoholismo, influyendo sobre dicha sensibilidad diferencial y, en última instancia, sobre el consumo de alcohol. En el presente trabajo se revisa la literatura experimental existente acerca de los elementos protagonistas en la relación entre estrés y etanol. Por una parte se revisan los principales modelos de estrés existentes y, por otra, se aborda el estudio de las propiedades reforzantes y aversivas de esta droga, incluyendo datos sobre la influencia de variables como la edad, el sexo, y la experiencia previa con la droga. Finalmente, se expone un resumen de los datos existentes sobre la investigación con animales sobre la influencia del estrés en la percepción de las propiedades motivacionales opuestas del etanol. Nuestro objetivo es contribuir a clarificar el conocimiento existente acerca de las relaciones entre determinados factores biológicos (como el sexo o la edad) y ambientales (experiencia previa y estrés), y la conducta de ingesta de alcohol, poniendo de manifiesto la importancia de algunos factores de riesgo para el desarrollo del alcoholismo. Palabras clave: Alcohol; estrés; refuerzo; aversión; adicción.Title: A review of experimental literature on alcohol´s motivational effects and its modulation by biological and environmental factors. Abstract: Alcohol is probably the most consumed psychoactive drug in the world. Controlled consumption of alcohol is common, but for many individuals this consumption becomes an addiction. The progression from an habitual consumption of alcohol to abuse of the substance could be due to the existence of a differential sensitivity, which would be genetically determined, to the reinforcing and aversive effects of alcohol. Likewise, it has been suggested that environmental factors such as stress might be involved in the onset of alcoholism, influencing on such a differential sensitivity and, ultimately, on the consumption of alcohol. In this paper it is reviewed the experimental published data on each of the elements of the relationship between stress and ethanol. Thus, on the one hand they are reviewed the main animals models of stress and, on the other hand, we approached the study of the reinforcing and aversive properties of ethanol, including data on the influence of variables such as age, sex, and previous experience with the drug. And, finally, we present a resume of data collected from animal research on the influence of stress on the perception of the motivational opposing properties of ethanol. Our purpose is help to clarify the existing knowledge about th...

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The role of kappa opioid receptors in stress‐induced reinstatement of alcohol seeking in rats

2014

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IntroductionStress is related to heavy alcohol use and relapse in alcoholics. Using the reinstatement model, we have shown that corticotropin-releasing factor (CRF) underlies stress-induced relapse to alcohol seeking in laboratory rodents. Little is known about how other neurotransmitters interact with CRF in these effects. Dynorphin and its receptor (kappa opioid receptor, KOR) are involved in stress responses and in alcohol seeking. KOR and CRF receptors (CRF R) may interact in the production of stress-related behaviors but it is not known whether this interaction is involved in reinstatement of alcohol seeking.MethodsMale Long Evans rats were trained to self-administer alcohol (12% w/v). After extinction of responding, we determined the effects of the KOR agonist, U50,488 (2.5, 5 mg/kg) on reinstatement of alcohol seeking, and their sensitivity to the selective KOR antagonist nor-binaltorphimine dihydrochloride (nor-BNI) (10 mg/kg) administered at different times before U50,488. We then examined the effects of nor-BNI on reinstatement induced by the stressor yohimbine (1.25 mg/kg) and on reinstatement induced by exposure to alcohol-associated cues. Finally, we determined whether CRF R1 blockade with antalarmin (10, 20 mg/kg) attenuates alcohol seeking induced by U50,488.ResultsU50,488 reinstated alcohol seeking. Prior treatment with nor-BNI 2, but not 24 h before administration of U50,488 or yohimbine blocked reinstatement induced by these drugs. Cue-induced reinstatement was blocked by nor-BNI administered 2 h prior to testing. Finally, U50,488-induced reinstatement was blocked by antalarmin.ConclusionsThese data further support a role for KOR in reinstatement of alcohol seeking under nonstress and stressful conditions and that KOR and CRF R interact in these effects.

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Endogenous kappa-opioid mediation of stress-induced potentiation of ethanol-conditioned place preference and self-administration

Abstract: These data demonstrated a stress-induced potentiation of the rewarding effects and self-administration of ethanol mediated by KOR signaling.

Cited by 117 publications

References 63 publications

Early-Life Social Isolation Stress Increases Kappa Opioid Receptor Responsiveness and Downregulates the Dopamine System

Early-Life Social Isolation Stress Increases Kappa Opioid Receptor Responsiveness and Downregulates the Dopamine System

Una revisión de la literatura experimental sobre los efectos motivacionales del alcohol y su modulación por factores biológicos y ambientales.

The role of kappa opioid receptors in stress‐induced reinstatement of alcohol seeking in rats

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