Ethanol exposure differentially alters pro-enkephalin mRNA expression in regions of the mesocorticolimbic system

Méndez, Milagros; Morales-Mulia, Marcela

doi:10.1007/s00213-006-0503-3

Cited by 33 publications

(29 citation statements)

References 38 publications

(56 reference statements)

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“…These lines of evidence support the hypothesis that reduction of A2AR-CREB activity in the DMS is critical to establish the reinforcing properties in the initial stages of habit formation. In addition, many alcohol preferring rodents exhibit lower enkephalin expression in the midbrain in comparison to non-preferring control animals and also have increased sensitivity to opioid alterations by ethanol treatment (Froehlich et al, 1991;Li et al, 1998;Mendez and Morales-Mulia, 2006;Ng et al, 1996). Thus, decreased CREB activity, possibly downstream of A2AR in the DMS, also promotes excessive ethanol seeking, which is governed by positive reinforcement and sensitivity to goal-directed responses during the extinction stage.…”

Section: A2ar Inhibition In the Dms And Goal Directed Drinkingmentioning

confidence: 99%

Adenosine Signaling in Striatal Circuits and Alcohol Use Disorders

Nam

Bruner

Choi

2013

Molecules and Cells

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Adenosine signaling has been implicated in the pathophysiology of alcohol use disorders and other psychiatric disorders such as anxiety and depression. Numerous studies have indicated a role for A1 receptors (A1R) in acute ethanol-induced motor incoordination, while A2A receptors (A2AR) mainly regulate the rewarding effect of ethanol in mice. Recent findings have demonstrated that dampened A2AR-mediated signaling in the dorsomedial striatum (DMS) promotes ethanol-seeking behaviors. Moreover, decreased A2AR function is associated with decreased CREB activity in the DMS, which enhances goal-oriented behaviors and contributes to excessive ethanol drinking in mice. Interestingly, caffeine, the most commonly used psychoactive substance, is known to inhibit both the A1R and A2AR. This dampened adenosine receptor function may mask some of the acute intoxicating effects of ethanol. Furthermore, based on the fact that A2AR activity plays a role in goal-directed behavior, caffeine may also promote ethanol-seeking behavior. The A2AR is enriched in the striatum and exclusively expressed in striatopallidal neurons, which may be responsible for the regulation of inhibitory behavioral control over drug rewarding processes through the indirect pathway of the basal ganglia circuit. Furthermore, the antagonistic interactions between adenosine and dopamine receptors in the striatum also play an integral role in alcoholism and addiction-related disorders. This review focuses on regulation of adenosine signaling in striatal circuits and the possible implication of caffeine in goal-directed behaviors and addiction.

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Section: A2ar Inhibition In the Dms And Goal Directed Drinkingmentioning

confidence: 99%

Adenosine Signaling in Striatal Circuits and Alcohol Use Disorders

Nam

Bruner

Choi

2013

Molecules and Cells

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“…However, DOP-R agonists reportedly have higher analgesic activity in states of disrupted physiological conditions (Kamei et al, 1994. Stressors, morphine, and ethanol administration change the distribution of DOP-R from the cytoplasmic compartment to the plasma membrane and increase DOP-R activity (Commons, 2003;Méndez et al, 2004Méndez et al, , 2008Hack et al, 2005;Méndez and Morales-Mulia, 2006). As it is difficult to directly demonstrate the redistribution of DOP-R using immunohistochemistry due to nonspecific activity of DOP-R antibodies (Scherrer et al, 2009), we measured the ex vivo activity of the DOP-R using […”

Section: Maintained Dop-r-mediated Analgesia With High Ethanol Consummentioning

confidence: 99%

δ-Opioid Receptor Function in the Dorsal Striatum Plays a Role in High Levels of Ethanol Consumption in Rats

Nielsen¹,

Simms²,

Li³

et al. 2012

J. Neurosci.

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Binge-like patterns of excessive drinking during young adulthood increase the propensity for alcohol use disorders (AUDs) later in adult life; however, the mechanisms that drive this are not completely understood. Previous studies showed that the ␦-opioid peptide receptor (DOP-R) is dynamically regulated by exposure to ethanol and that the DOP-R plays a role in ethanol-mediated behaviors. The aim of this study was to determine the role of the DOP-R in high ethanol consumption from young adulthood through to late adulthood by measuring DOP-R-mediated [ 35 S]GTP␥S binding in brain membranes and DOP-R-mediated analgesia using a rat model of high ethanol consumption in Long Evans rats. We show that DOP-R activity in the dorsal striatum and DOP-R-mediated analgesia changes during development, being highest during early adulthood and reduced in late adulthood. Intermittent access to ethanol but not continuous ethanol or water from young adulthood leads to an increase in DOP-R activity in the dorsal striatum and DOP-R-mediated analgesia into late adulthood. Multiple microinfusions of naltrindole into the dorsal striatum or multiple systemic administration of naltrindole reduces ethanol consumption, and following termination of treatment, DOP-R activity in the dorsal striatum is attenuated. These findings suggest that DOP-R activity in the dorsal striatum plays a role in high levels of ethanol consumption and suggest that targeting the DOP-R is an alternative strategy for the treatment of AUDs.

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“…La administración de una dosis alta de etanol (2.5g/kg) disminuyó la expresión del ARNm de Pro-enk en el ATV y la SN (pars compacta [SNc] y SNr) de ratas Wistar, y la incrementó en la corteza prefrontal. 46,47 De manera interesante, este tratamiento produce un aumento prolongado y sostenido en los niveles del ARNm de Pro-enk en el NAcc, tanto en el core como en el shell, 46 así como en distintas zonas del CP. 47 La administración de etanol también produce aumentos en la expresión de este ARNm en otras áreas cerebrales, como el núcleo paraventricular del hipotálamo, mientras que en otras, como el giro dentado y las regiones CA1, CA2 y CA3 del hipocampo, el etanol induce efectos bifásicos.…”

Section: Efectos Agudos Y Crónicos Del Etanol Sobre Los Sistemas Enceunclassified

“…El conjunto de estos estudios indica que el sistema encefalinérgico es uno de los blancos importantes del etanol en el cerebro y la liberación de Met-enk inducida por etanol es uno de los eventos clave en esas acciones (para revisiones, ver Méndez y Morales-Mulia 2008b,c). 45,50 Estos estudios sugieren, además, que las encefalinas desempeñan un papel crucial en el reforzamiento de etanol. La modulación de la transmisión DAérgica por opioides en el sistema mesocorticolímbico es, indudablemente, parte importante de este proceso.…”

Section: Efectos Agudos Y Crónicos Del Etanol Sobre Los Sistemas Enceunclassified

Participación de los sistemas endógenos de péptidos opioides en los mecanismos de reforzamiento y dependencia al alcohol

Méndez¹

2013

Salud Ment

Self Cite

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Evidencias bioquímicas y conductuales indican que el sistema dopaminérgico mesolímbico cumple un papel fundamental en los mecanismos de reforzamiento y recompensa del alcohol (etanol) y otras drogas de abuso. Se ha propuesto también que la actividad de la vía dopaminérgica nigroestriatal determina la sensibilidad cerebral a etanol, lo que parece estar directamente relacionado con los procesos de adicción a la droga. Además de la dopamina, varios neurotransmisores y neuromoduladores están implicados en los mecanismos de reforzamiento del etanol, entre ellos, el ácido gama-aminobutírico (GABA), el glutamato, la serotonina, la acetilcolina y los péptidos opioides (encefalinas, endorfinas y dinorfinas). El alcohol y los opioides comparten características farmacológicas y exhiben efectos similares sobre el comportamiento en animales y en el hombre. Éstos y otros estudios sugieren que las propiedades reforzadoras del etanol se deben, al menos parcialmente, a la activación de los sistemas endógenos de péptidos opioides, proceso que es inducido por el propio alcohol. Esta activación podría, a su vez, aumentar el valor hedónico y los efectos reforzadores de la droga. Los cambios inducidos por etanol sobre la transmisión de opioides podrían contribuir de manera importante a los procesos de intoxicación y a las respuestas neuronales adaptativas que produce el consumo prolongado de la droga. La transmisión opioidérgica puede ser afectada por etanol a distintos niveles, incluyendo la biosíntesis, liberación e inactivación de los opioides endógenos, así como la unión de éstos a sus receptores. Numerosas evidencias sugieren que los receptores opioides mu y delta desempeñan un papel fundamental en el reforzamiento y la dependencia al etanol. Así, las encefalinas y la ß-endorfina actuarían como mediadores fisiológicos de las acciones del etanol en el cerebro, desempeñando un papel crucial en las conductas de alto consumo de la droga. En los últimos años, nuestro grupo se ha centrado en investigar el papel de los sistemas endógenos de péptidos opioides en estos procesos. Las evidencias obtenidas en nuestro laboratorio sugieren que las encefalinas y la ß-endorfina participan en forma diferencial y selectiva en el reforzamiento y la dependencia al etanol.

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Ethanol exposure differentially alters pro-enkephalin mRNA expression in regions of the mesocorticolimbic system

Abstract: Our results indicate that enkephalin expression in regions of the rat mesocorticolimbic system is differentially altered by acute ethanol treatment and suggest that enkephalins may play a key role in ethanol reinforcement mechanisms.

Cited by 33 publications

References 38 publications

Adenosine Signaling in Striatal Circuits and Alcohol Use Disorders

Adenosine Signaling in Striatal Circuits and Alcohol Use Disorders

δ-Opioid Receptor Function in the Dorsal Striatum Plays a Role in High Levels of Ethanol Consumption in Rats

Participación de los sistemas endógenos de péptidos opioides en los mecanismos de reforzamiento y dependencia al alcohol

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