Aversive Effects of Ethanol in Adolescent Versus Adult Rats: Potential Causes and Implication for Future Drinking (original) (raw)
Related papers
Developmental Psychobiology, 2010
Age-related patterns of sensitivity to appetitive and aversive stimuli seemingly have deep evolutionary roots, with marked developmental transformations seen during adolescence in a number of relatively ancient brain systems critical for motivating and directing reward-related behaviors. Using a simple animal model of adolescence in the rat, adolescents have been shown to be more sensitive than their adult counterparts to positive rewarding effects of alcohol, other drugs, and certain natural stimuli, while being less sensitive to the aversive properties of such stimuli. Adolescent-typical alcohol sensitivities may be exacerbated further by a history of prior stress or alcohol exposure as well as by genetic vulnerabilities, permitting relatively high levels of adolescent alcohol use and perhaps an increased probability for the emergence of abuse disorders. A number of potential (albeit tentative) implications of these basic research findings for prevention science are considered.
Background: Binge alcohol drinking during adolescence is a serious health problem that may increase future risk of an alcohol use disorder. Although there are several different procedures by which to preclinically model binge-like alcohol intake, limited-access procedures offer the advantage of achieving high voluntary alcohol intake and pharmacologically relevant blood alcohol concentrations (BACs). Therefore, in the current study, developmental differences in binge-like alcohol drinking using a limited-access cycling procedure were examined. In addition, as alcohol drinking has been negatively correlated with sensitivity to the aversive properties of alcohol, we examined developmental differences in sensitivity to an alcohol-induced conditioned taste aversion (CTA).
Alcoholism: Clinical and Experimental Research, 2011
Background-Given the prevalence of alcohol use in adolescence, it is important to understand the consequences of chronic ethanol exposure during this critical period in development. The purpose of the present study was to assess possible age-related differences in susceptibility to tolerance development to ethanol-induced sedation and withdrawal-related anxiety, as well as voluntary ethanol intake after chronic exposure to relatively high doses of ethanol during adolescence or adulthood. Methods-Adolescent and adult male Sprague-Dawley rats were assigned to one of five 10 day exposure conditions: chronic ethanol (4 g/kg every 48 hours), chronic saline (equivalent volume every 24 hours), chronic saline/acutely challenged with ethanol (4 g/kg on day 10), nonmanipulated/acutely challenged with ethanol (4 g/kg on day 10) or non-manipulated. For assessment of tolerance development, loss of righting reflex was tested on the first and last ethanol exposure days in the chronic ethanol group, with both saline and non-manipulated animals likewise challenged on the last exposure day. Withdrawal-induced anxiety was indexed in a social interaction test 24 hrs after the last ethanol exposure, with ethanol-naïve chronic saline and nonmanipulated animals serving as controls. Voluntary intake was assessed 48 hours after the chronic exposure period in chronic ethanol, chronic saline and non-manipulated animals using an 8 day 2 bottle choice, limited access ethanol intake procedure. Results-Adolescents were less sensitive to the sedative effects of ethanol than adults. Adults, but not adolescents, developed chronic tolerance to the sedative effects of ethanol, tolerance that appeared to be metabolic in nature. Social deficits were observed after chronic ethanol in both adolescents and adults. Adolescents drank significantly more ethanol than adults on a g/kg basis, with intake uninfluenced by prior ethanol exposure at both ages. Conclusion-Adolescents and adults may differ in their ability and/or propensity to adapt to chronic ethanol exposure, with adults, but not adolescents, developing chronic metabolic tolerance. However, this chronic exposure regimen was sufficient to disrupt baseline levels of social behavior at both ages. Taken together, these results suggest that, despite the age-related differences in tolerance development, adolescents are as susceptible as adults to consequences of chronic ethanol exposure, particularly in terms of disruptions in social behavior. Whether these effects would last into adulthood remains to be determined.
Ethanol induces second-order aversive conditioning in adolescent and adult rats
Alcohol, 2011
Alcohol abuse and dependence is considered a developmental disorder with etiological onset during late childhood and adolescence, and understanding age-related differences in ethanol sensitivity is important. Low to moderate ethanol doses (0.5 and 2.0 g/kg, i.g.) induce single-trial, appetitive second-order place conditioning (SOC) in adolescent, but not adult, rats. Recent studies have demonstrated that adolescents may be less sensitive than adults to the aversive properties of ethanol, reflected by conditioned taste aversion. The present study assessed the aversive motivational effects of high-dose ethanol (3.0 and 3.25 g/kg, i.g., for adolescent and adults, respectively) using SOC. These doses were derived from Experiment 1, which found similar blood and brain ethanol levels in adolescent and adult rats given 3.0 and 3.25 g/kg ethanol, respectively. In Experiment 2, animals received ethanol or vehicle paired with intraoral pulses of sucrose (conditioned stimulus 1 [CS1]). After one, two, or three conditioning trials, rats were presented with the CS1 while in a distinctive chamber (CS2). When tested for CS2 preference, ethanoltreated animals exhibited reduced preference for the CS2 compared with controls. This result, indicative of ethanol-mediated aversive place conditioning, was similar for adolescents and adults, for females and males, and after one, two, or three training trials. One finding, however, suggested that adolescents were less sensitive than adults to ethanol's aversive effects at the intermediate level of training. In conjunction with previous results, the present study showed that in adolescent rats subjected to SOC, ethanol's hedonic effects vary from appetitive to aversive as the ethanol dose increases. Adolescent and adult animals appear to perceive the post-ingestive effects of highdose ethanol as similarly aversive when assessed by SOC.
Genetic and early environmental contributions to alcohol's aversive and physiological effects
Pharmacology Biochemistry and Behavior, 2008
Genetic and early environmental factors interact to influence ethanol's motivational effects. To explore these issues, a reciprocal cross-fostering paradigm was applied to Fischer and Lewis rats. The adult female offspring received vehicle or the kappa opioid antagonist nor-BNI (1 mg/kg) followed by assessments of conditioned taste aversion (CTA), blood alcohol concentrations (BACs) and hypothermia induced by 1.25 g/kg intraperitoneal ethanol. CTA acquisition in the in-fostered Fischer and Lewis animals did not differ; however, the Fischer maternal environment produced stronger acquisition in the cross-fostered Lewis rats versus their in-fostered counterparts. CTAs in the Fischer rats were not affected by cross-fostering. In extinction, the in-fostered Lewis animals displayed stronger aversions than the Fischer groups on two trials (of 12) whereas the cross-fostered Lewis differed from the Fischer groups on nine trials. Despite these CTA effects, Lewis rats exhibited higher BACs and stronger hypothermic responses than Fischer with no cross-fostering effects in either strain. No phenotypes were affected by nor-BNI. These data extend previous findings dissociating the aversive and peripheral physiological effects of ethanol in female Fischer and Lewis rats, and highlight the importance of genetic and early environmental factors in shaping subsequent responses to alcohol's motivational effects in adulthood.
Alcoholism-clinical and Experimental Research, 2007
Background: Initial ingestion of ethanol by naïve rats has seemed to decrease dramatically with age. During the preweanling period, infant rats consume large quantities of high concentrations of ethanol without initiating procedures, in some instances exceeding doses required for severe motor incoordination. During adulthood, however, initial ingestion of ethanol without initiation procedures is low and infrequent. In the present study, the ontogeny of ethanol intake was measured in juvenile, adolescent and adult rats using a technique [consume off the floor (COF)] similar to that used to study intake during infancy. How this initial experience with ethanol affected subsequent affinity for ethanol intake was later assessed using 2-bottle choice preference tests.Methods: Independent ingestion of ethanol was measured at 3 developmental periods, the juvenile period (P22–P28), adolescence (P30–P34) and adulthood (P60–P64), with systematic variation in ethanol concentration (15 or 30% v/v) and palatability (sweetness) of ethanol. Blood ethanol concentrations (BECs) were determined in all animals. This dependent variable served as an estimate of absolute ethanol ingestion. Three COF sessions were conducted for each age group. Following these sessions animals' ethanol consumption was also assessed using a 2-bottle choice test (water vs 15% v/v unsweetened ethanol).Results: In all experiments, groups consuming 30% v/v ethanol exhibited significantly higher BECs than those exposed to 15% v/v ethanol. Adding saccharin to the ethanol increased absolute ethanol ingestion in only the oldest animals. During the pre-exposure phase (COF sessions) of each experiment, absolute ethanol intake was found to decline with repeated exposures. Sex effects were particularly evident during later stages of ontogeny (adolescents and adults). The overall pattern of results indicated that juveniles relative to adults show a marked predisposition to consume highly concentrated ethanol solutions and that BECs derived from the COF sessions influenced ethanol acceptance patterns in the subsequent 2-bottle test.Conclusions: Using the (COF) technique with BECs as an estimate of intake, absolute ethanol consumption seems to be quite high early in ontogeny and decline gradually into adulthood. Adding saccharin to ethanol solutions at the concentration used in the present study (0.1%) was generally not sufficient to increase absolute ethanol intake from the floor, except during adulthood. The experimental strategy employed in this study represents a novel approach for examining ethanol acceptance patterns across ontogeny and how experience with the process of intoxication affects subsequent ethanol preferences.
Alcoholism: Clinical and Experimental Research, 2009
Background: Animal behavioral models of voluntary ethanol consumption represent a valuable tool to investigate the relationship between age and propensity to consume alcohol using an experimental methodology. Although adolescence has been considered as a critical age, few are the studies that consider the preadolescence age. This study examines the ethanol consumption ⁄ preference and the propensity to show an alcohol deprivation effect (ADE) after a short voluntary ethanol exposure from a developmental perspective. Methods: Three groups of heterogeneous Wistar rats of both sexes with ad libitum food and water were exposed for 10 days to 3 ethanol solutions at 3 different ontogenetic periods: preadolescence (PN19), adolescence (PN28), and adulthood (PN90). Ethanol intake (including circadian rhythm), ethanol preference, water and food consumption, and ADE were measured. Results: During the exposure, the 3 groups differed in their ethanol intake; the greatest amount of alcohol (g ⁄ kg) was consumed by the preadolescent rats while the adolescents showed a progressive decrease in alcohol consumption as they approached the lowest adult levels by the end of the assessed period. The pattern of ethanol consumption was not fully explained in terms of hyperphagia and ⁄ or hyperdipsia at early ages, and showed a wholly circadian rhythm in adolescent rats. After an abstinence period of 7 days, adult rats showed an ADE measured both as an increment in ethanol consumption and preference, whereas adolescent rats only showed an increment in ethanol preference. Preadolescent rats decreased their consumption and their preference remained unchanged. Conclusions: In summary, using a short period of ethanol exposure and a brief deprivation period the results revealed a direct relationship between chronological age and propensity to consume alcohol, being the adolescence a transition period from the infant to the adult pattern of alcohol consumption. Preadolescent animals showed the highest ethanol consumption level. The ADE was only found in adult animals for both alcohol consumption and preference, whereas adolescents showed an ADE only for preference. No effect of sex was detected in any phase of the experiment.