Ethanol‐Induced Conditioned Taste Aversion in Male Sprague‐Dawley Rats: Impact of Age and Stress

Abstract

Background Age-specific characteristics may contribute to the elevation in ethanol intake commonly reported among adolescents compared to adults. The present study was designed to examine age-related differences in sensitivity to ethanol’s aversive properties using a conditioned taste aversion (CTA) procedure with sucrose serving as the conditioned stimulus. Given that ontogenetic differences in responsiveness to stressors have been previously reported, the role of stressor exposure on the development of CTA was also assessed. Methods Experiment 1 examined the influence of 5 days of prior restraint stress exposure on the expression of CTA in a 2-bottle test following 1 pairing of a sucrose solution with ethanol. In Experiment 2, the effects of 7 days of social isolation on the development of CTA were observed using a 1-bottle test following multiple sucrose-ethanol pairings. Results The present study revealed age-related differences in the development of ethanol-induced CTA. In Experiment 1, adolescents required a higher dose of ethanol than adults to demonstrate an aversion. In Experiment 2, adolescents required not only a higher ethanol dose but also more pairings of ethanol with the sucrose conditioned stimulus. No effects of prior stressor exposure were observed in either experiment. Conclusions Together, these experiments demonstrate an adolescent-specific insensitivity to the aversive properties of ethanol that elicit CTA, a pattern not influenced by repeated restraint stress or housing in social isolation. This age-related insensitivity to the dysphoric effects of ethanol is consistent with other work from our laboratory, adding further to the evidence that adolescent rats are less susceptible to negative consequences of ethanol that may serve as cues to curb consumption.

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

“…De hecho, la mayor parte de los estudios, realizados tanto con humanos (revisado en Song et al, 2007), como con animales (ver Anderson, Varinskaya y Spear, 2010;Doremus et al, 2005;Garcia-Burgos et al, 2009;Song et al, 2007;Vetter-O´Hagen et al, 2009), indican que los individuos adolescentes consumen mayores cantidades de alcohol que los adultos, probablemente debido a diferencias en los niveles hormonales y de neuroadaptación.…”

“…Los datos recopilados a partir de estas investigaciones parecen indicar que los adolescentes, en general, son menos sensibles a una amplia gama de efectos sedativos (narcosis, coordinación motora, etc. ), aversivos y estimulantes del etanol (por ejemplo, sensibilización conductual) (Vetter-O´Hagen et al, 2009;Anderson et al, 2010), pero sí muestran mayor afectación cognitiva después del tratamiento con la droga, y mayor sensibilidad a los efectos positivos reforzantes del etanol, evaluados mediante CPL (revisado en Pautassi et al, 2010).…”

“…En la misma línea, Anderson et al (2010) han informado que las ratas adolescentes empleadas en su estudio, no sólo requirieron una mayor dosis de etanol para inducir CAG, sino también un mayor número de emparejamientos entre el estímulo condicionado y el etanol. Estos datos parecen poner de manifiesto la existencia de una insensibilidad específica de los individuos adolescentes a las propiedades aversivas del etanol capaces de inducir CAG.…”

Adolescent rats fail to demonstrate a LiCl-induced pre-exposure effect: Implications for the balance of drug reward and aversion in adolescence

“…Although initially demonstrated with X-irradiation, such learning has been demonstrated with a wide variety of drugs ranging from classic emetics such as lithium chloride (LiCl) and apomorphine (Garcia et al, 1966) to drugs of abuse such as amphetamine (Booth et al, 1977) and morphine (Farber et al, 1976). Although taste avoidance learning is generally robust and rapidly acquired, it is affected by a variety of subject characteristics (age: Anderson et al, 2010;Schramm-Sapyta et al, 2009;sex: Carroll et al, 2004;Vetter-O'Hagen et al, 2009;strain: Davis & Riley, 2007;Kosten et al, 1994) and experimental manipulations (light/dark cycle, stress: Gomez et al, 2000;Sperling et al, 2010, route of administration and drug dose : Ferrari et al, 1991).…”

“…This is of interest given that there are age-dependent differences in taste avoidance conditioning with a number of compounds (Doremus-Fitzwater et al, 2010;Merluzzi et al, 2014;Schramm-Sapyta et al, 2009). For example, adolescent rats consistently display weaker drug-induced CTA compared to adults when conditioned with a number of different compounds such as amphetamine (Infurna & Spear, 1979), cocaine (Schramm-Sapyta et al, 2006), ethanol (SchrammSapyta et al, 2010Vetter-O'Hagen et al, 2009), morphine , and nicotine (Wilmouth and Spear, 2004;Shram et al, 2006), among others (Anderson et al, 2010;Anderson et al, 2014;Flax et al, 2015;Schramm-Sapyta et al, 2007;Wetzel et al, 2014). The relatively weaker taste avoidance reported in adolescents has been suggested to be a function of their relative insensitivity to the drug's aversive effects (Schramm-Sapyta et al, 2014), i.e., the drug is less aversive in adolescent subjects and thus induces a weaker avoidance response.…”