Aversive Effects of Ethanol in Adolescent Versus Adult Rats: Potential Causes and Implication for Future Drinking

Abstract

Background Many people experiment with alcohol and other drugs of abuse during their teenage years. Epidemiological evidence suggests that younger initiates into drug taking are more likely to develop problematic drug seeking behavior, including binge and other high-intake behaviors. The level of drug intake for any individual depends on the balance of rewarding and aversive effects of the drug in that individual. Multiple rodent studies have demonstrated that aversive effects of drugs of abuse are reduced in adolescent compared to adult animals. In the present study we addressed two key questions: First, do reduced aversive effects of ethanol in younger rats correlate with increased ethanol consumption? Second, are the reduced aversive effects in adolescents attributable to reduced sensitivity to ethanol's physiological effects? Methods Adolescent and adult rats were tested for ethanol conditioned taste aversion followed by a voluntary drinking period, including post-deprivation consumption. Multivariate regression was used to assess correlations. In separate experiments, adolescent and adult rats were tested for their sensitivity to the hypothermic and sedative effects of ethanol, and for blood ethanol concentrations (BECs). Results We observed that in adolescent rats but not adults, taste aversion was inversely correlated with post-deprivation consumption. Adolescents also exhibited a greater increase in consumption after deprivation than adults. Furthermore, the age difference in ethanol conditioned taste aversion was not attributable to differences in hypothermia, sedation, or BECs. Conclusions These results suggest that during adolescence, individuals that are insensitive to aversive effects are most likely to develop problem drinking behaviors. These results underscore the importance of the interaction between developmental stage and individual variation in sensitivity to alcohol.

The ontogeny of ethanol aversion

“…While there is convincing evidence from both our laboratory and others that mid-adolescents are less sensitive to CTA to ethanol than are adults (Anderson et al, 2010; Holstein, Spanos, & Hodge, 2011; Schramm-Sapyta et al, 2010; C. Vetter-O’Hagen et al, 2009), the precise ontogeny of these aversive properties has yet to be identified.…”

Emergence of sex differences in the development of substance use and abuse during adolescence

“…Multiple laboratories have used conditioned taste aversion or conditioned place aversion to show that adolescent rodents are less likely to avoid a taste or place paired with a dose of drug than adults. This is true for every drug that has been tested including alcohol, nicotine, THC, cocaine, amphetamine, narcotics and even LiCl, the prototype GI irritant that is used as a control in these studies (Acevedo, Molina, Nizhnikov, Spear, & Pautassi, 2010; Anderson, Agoglia, Morales, Varlinskaya, & Spear, 2012; Anderson, Morales, Spear, & Varlinskaya, 2013; Anderson, Varlinskaya, & Spear, 2010; Carvalho, Reyes, Ramalhosa, Sousa, & Van Bockstaele, 2014; Drescher, Foscue, Kuhn, & Schramm-Sapyta, 2011; Hurwitz, Merluzzi, & Riley, 2013; Natarajan et al, 2011; Pandolfo, Vendruscolo, Sordi, & Takahashi, 2009; Philpot et al, 2003; Schramm-Sapyta et al, 2007; Schramm-Sapyta et al, 2010; Schramm-Sapyta et al, 2014; Schramm-Sapyta, Morris, & Kuhn, 2006; Sherrill, Berthold, Koss, Juraska, & Gulley, 2011; Shram, Siu, Li, Tyndale, & Le, 2008; Vetter-O'Hagen et al, 2009). The latter finding suggests that the lack of conditioned taste aversion reflects a fundamental aspect of how the adolescent brain processes aversive input rather than a characteristic of any particular drug.…”

Consequences of Adolescent or Adult Ethanol Exposure on Tone and Context Fear Retention: Effects of an Acute Ethanol Challenge During Conditioning

“…For instance, adolescents are less sensitive to several acute ethanol effects, such as ethanol-induced motor impairment (Broadwater et al, 2011a; Ramirez & Spear, 2010; White et al, 2002b) and conditioned taste aversion (CTA) (Anderson et al, 2010; Schramm-Sapyta et al, 2010), factors that may contribute to adolescents’ ability and/or propensity to consume large amounts of alcohol relative to their more mature counterparts (e.g., Brunell & Spear, 2005; Doremus et al, 2005; Vetter et al, 2007; Vetter-O’Hagen et al, 2009). Interestingly, these adolescent-typical attenuations in sensitivity to both the motor impairing (White et al, 2002a) and aversive (Diaz-Granados & Graham, 2007; Sherrill et al, 2011) effects of ethanol have been found to persist into adulthood after exposure to alcohol during adolescence.…”