Ethanol drinking in rodents: is free-choice drinking related to the reinforcing effects of ethanol?

Abstract

Many studies have used voluntary ethanol consumption by animals to assess the influence of genetic and environmental manipulations on ethanol drinking. However, the relationship between home cage ethanol consumption and more formal assessments of ethanol-reinforced behavior using operant and instrumental conditioning procedures is not always clear. The present review attempted to evaluate whether there are consistent correlations between mouse and rat home cage ethanol drinking on the one hand, and either operant oral self-administration (OSA), conditioned taste aversion (CTA) or conditioned place preference (CPP) with ethanol on the other. We also review literature on intravenous ethanol self-administration (IVSA). To collect data, we evaluated a range of genetic manipulations that can change both genes and ethanol drinking behavior including selective breeding, transgenic and knock-out models, and inbred and recombinant inbred strain panels. For a genetic model to be included in the analysis, there had to be published data resulting in differences on home cage drinking and data for at least one of the other behavioral measures. A consistent, positive correlation was observed between ethanol drinking and OSA, suggesting that instrumental behavior is closely genetically related to consummatory and ingestive behavior directed at ethanol. A negative correlation was observed between CTA and drinking, suggesting that ethanol's aversive actions may limit oral consumption of ethanol. A more modest, positive relationship was observed between drinking and CPP, and there were not enough studies available to determine a relationship with IVSA. That some consistent outcomes were observed between widely disparate behavioral procedures and genetic populations may increase confidence in the validity of findings from these assays. These findings may also have important implications when researchers decide which phenotypes to use in measuring alcohol-reward relevant behaviors in novel animal models.

Viral-Mediated Knockdown of mGluR7 in the Nucleus Accumbens Mediates Excessive Alcohol Drinking and Increased Ethanol-Elicited Conditioned Place Preference in Rats

“…Rats receiving these microinjections were more sensitive to the rewarding effects of ethanol. Considering that the enhanced preference to drug-paired environments and rewarding effects of psycho-stimulants appear to depend on common neural substrates (Green and Grahame, 2008;McBride et al, 1999;Risinger et al, 1994;Vlachou and Markou, 2010), these findings raised the possibility that reduced expression of mGlu7 receptors in the mesolimbic system would also affect the rewarding effects of ethanol. Indeed, lower doses of alcohol established-conditioned-place preferences in rats given this treatment, suggesting that these rats were more sensitive to the rewarding effects of the drug.…”

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

“…Cabe mencionar, no obstante, que dada la naturaleza del etanol, y su capacidad para inducir efectos reforzantes y aversivos, es frecuente obtener aprendizaje de aversión, en lugar de preferencia, por un lugar en ratas (no tanto en ratones), sobre todo si la dosis de etanol es superior a 1 gr/kg (ver Green y Grahame, 2008). No obstante, las condiciones bajo las cuales los animales desarrollan preferencia o aversión por un lugar dependen de muchos factores, como la vía de administración (intaperitoneal, intragástrica, consumo forzado, etc.…”

“…29, nº 3 (octubre) cuentan con la capacidad de generar tanto efectos reforzantes como aversivos, habiéndose sugerido que la vulnerabilidad a las drogas de abuso no está sólo determinada por la sensibilidad al refuerzo, sino que puede ser el resultado del balance entre los efectos motivacionales opuestos producidos por la droga (revisado en Roma, Davis, Kohut, Huntsberry y Riley, 2008). De hecho, las consecuencias apetitivas y aversivas del etanol incrementan y decrecen, respectivamente, la probabilidad subsecuente de las conductas de búsqueda y consumo de alcohol (revisado en Pautassi, Nizhnikov y Spear, 2009;Wilson, Burghardt, Ford, Wilkinson y Primeaux, 2004;ver también Cunningham, Clemans y Fidler, 2002;Broadbent, Muccino y Cunningham, 2002;Green y Grahame, 2008). El estudio de estos factores motivacionales parece ser particularmente importante para la comprensión de por qué ciertos individuos progresan rápidamente desde un uso controlado del alcohol, al abuso y la dependencia, mientras que otros continúan con el consumo controlado a pesar de la continua exposición a la droga.…”

Neurogenetic studies of alcohol addiction

“…Interestingly, although there was a strong and consistent association between home cage drinking and intravenous self-administration across genotypes, there was a weaker association between these consummatory responses and the efficacy of ethanol to condition a place preference. The place preference data are complicated by a species difference: whereas mice prefer ethanol-associated locations, rats generally learn to avoid them, for reasons as yet not understood (Green & Grahame 2008). An older study of several inbred mouse strains documented differences in their ability to withhold a rewarded nose poke response for a few seconds.…”

“…There is good agreement that high drinkers tend to develop tolerance more readily than non-drinkers, and that it persists longer. As noted in analyses of inbred strain panels, the relationship between ethanol-induced CTA and drinking is shared across selections (Phillips et al 2005;Green & Grahame 2008). Finally, mice were bred from the F2 cross of C57BL /6J!DBA/2J in a short-term selection for high-or low-preference drinking.…”