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1.
Brain Res Bull ; 138: 20-25, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-28778837

RESUMEN

Adolescence is a critical period in brain development that coincides with the initiation of alcohol use. Nicotinic acetylcholine receptors (nAChR) have been shown to modulate ethanol behaviors in adult humans and in animal models; however, the role of these receptors in adolescent ethanol behaviors has not been explored. Throughout adolescence, nAChR expression undergoes large-scale developmental changes which may alter behavioral responses to ethanol. Here we examined the effect of varenicline, a nAChR partial agonist, on ethanol consumption, ataxia, sedation, and metabolism in adolescent male and female C57BL/6J mice. The effect of varenicline on ethanol consumption was tested through the Drinking-in-the-Dark (DID) paradigm that models binge-like ethanol consumption. To ensure that results were specific for ethanol, we also tested the effect of varenicline on saccharin consumption. Additionally, varenicline was administered 30min prior to an acute injection of ethanol before being tested for ataxia on the balance beam, sedation using the loss of righting reflex, or ethanol metabolism. Varenicline dose dependently decreased ethanol consumption, but also influenced saccharin intake. Varenicline showed no significant effect on ethanol metabolism, ataxia, or sedation. Unlike its effects in adult animals, varenicline is able to reduce ethanol consumption without increasing the ataxic and sedative effects of ethanol. This work suggests that the neurobiological mechanisms of ethanol behaviors may change across the lifespan and highlights the need for more research on the role of nAChRs in ethanol behaviors throughout development.


Asunto(s)
Consumo de Bebidas Alcohólicas/tratamiento farmacológico , Depresores del Sistema Nervioso Central/administración & dosificación , Etanol/administración & dosificación , Agonistas Nicotínicos/farmacología , Sacarina/administración & dosificación , Edulcorantes/administración & dosificación , Vareniclina/farmacología , Factores de Edad , Análisis de Varianza , Animales , Animales Recién Nacidos , Relación Dosis-Respuesta a Droga , Etanol/metabolismo , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Equilibrio Postural/efectos de los fármacos , Reflejo de Enderezamiento/efectos de los fármacos
2.
Alcohol ; 61: 43-49, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28457669

RESUMEN

Nicotinic acetylcholine receptors (nAChRs) in the mesolimbic dopamine system have been implicated in ethanol behaviors. In particular, work in genetically engineered mice has demonstrated that α6-containing nAChRs are involved in ethanol consumption and sedation. A limitation of these studies is that the alteration in the receptor was present throughout development. The recently described α6ß2 antagonist, N,N-decane-1,10-diyl-bis-3-picolinium diiodide (bPiDI), now makes it possible to test for the involvement of these receptors using a pharmacological approach. The aim of this study was to examine the role of α6ß2 nAChRs in ethanol behaviors using a pharmacological approach. Adolescent C57BL/6J mice were treated with bPiDI 30 min prior to testing the mice for binge-like ethanol consumption in the drinking-in-the-dark (DID) test, ethanol-induced motor incoordination using the balance beam, and ethanol-induced sedation using the Loss of Righting Reflex (LORR) paradigm. Adolescent animals were chosen because they express a high amount of α6 mRNA relative to adult animals. Control studies were also performed to determine the effect of bPiDI on locomotor activity and ethanol metabolism. Female mice treated with 20 mg/kg bPiDI had reduced locomotor activity compared to saline-treated animals during the first 30 min following an acute injection. Pretreatment with the α6ß2 antagonist reduced adolescent ethanol consumption but also reduced saccharin consumption. No significant effects were observed on ethanol-induced ataxia, sedation, or metabolism. This study provides evidence that α6ß2 nAChRs are involved in locomotor activity as well as ethanol and saccharin consumption in adolescent animals.


Asunto(s)
Consumo de Bebidas Alcohólicas/fisiopatología , Etanol/administración & dosificación , Locomoción/efectos de los fármacos , Receptores Nicotínicos/fisiología , Consumo de Bebidas Alcohólicas/prevención & control , Animales , Consumo Excesivo de Bebidas Alcohólicas/fisiopatología , Etanol/efectos adversos , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Antagonistas Nicotínicos/farmacología , Picolinas/farmacología , Compuestos de Piridinio/farmacología , Sacarina/administración & dosificación
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