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Chronic Drinking During Adolescence Predisposes the Adult Rat for Continued Heavy Drinking: Neurotrophin and Behavioral Adaptation after Long-Term, Continuous Ethanol Exposure.

ABSTRACT: Previous research has found that adolescent ethanol (EtOH) exposure alters drug seeking behaviors, cognition and neuroplasticity. Using male Sprague Dawley rats, differences in spatial working memory, non-spatial discrimination learning and behavioral flexibility were explored as a function of age at the onset (mid-adolescent vs. adult) of chronic EtOH exposure (CET). Concentrations of mature brain-derived neurotrophic factor (mBDNF) and beta-nerve growth factor (?-NGF) in the prefrontal cortex and hippocampus were also assessed at different time-points: during CET, following acute abstinence (48-hrs), and after protracted abstinence (6-8 wks). Our results revealed that an adolescent onset of CET leads to increased EtOH consumption that persisted into adulthood. In both adult and adolescent onset CET groups, there were significant long-term reductions in prefrontal cortical mBDNF and ?-NGF levels. However, only adult onset CET rats displayed decreased hippocampal BDNF levels. Spatial memory, assessed by spontaneous alternation and delayed alternation, was not significantly affected by CET as a function of age of drinking onset, but higher blood-EtOH levels were correlated with lower spontaneous alternation scores. Regardless of the age of onset, EtOH exposed rats were impaired on non-spatial discrimination learning and displayed inflexible behavioral patterns upon reversal learning. Our results indicate that adolescent EtOH exposure changes long-term consumption patterns producing behavioral and neural dysfunctions that persist across the lifespan.

SUBMITTER: Fernandez GM

PROVIDER: S-EPMC4773001 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Chronic Drinking During Adolescence Predisposes the Adult Rat for Continued Heavy Drinking: Neurotrophin and Behavioral Adaptation after Long-Term, Continuous Ethanol Exposure.

Fernandez Gina M GM Stewart William N WN Savage Lisa M LM

PloS one 20160301 3

Previous research has found that adolescent ethanol (EtOH) exposure alters drug seeking behaviors, cognition and neuroplasticity. Using male Sprague Dawley rats, differences in spatial working memory, non-spatial discrimination learning and behavioral flexibility were explored as a function of age at the onset (mid-adolescent vs. adult) of chronic EtOH exposure (CET). Concentrations of mature brain-derived neurotrophic factor (mBDNF) and beta-nerve growth factor (β-NGF) in the prefrontal cortex ...[more]

PMID: 26930631

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Project description:Epidemiological studies suggest that binge drinking is prevalent among adolescents, and may result in neurobehavioral consequences. Animal models provide the experimental control to investigate the consequences of "binge" alcohol exposure during this neurodevelopmental epoch. The current study used an animal model that combined an intermittent pattern of alcohol vapor exposure with voluntary drinking of 20% unsweetened alcohol in adolescent male and female Wistar rats (postnatal day [PD] 22-62), in order to test for potential differences in behavioral changes, ethanol drinking, and hypocretin/orexin (Hcrt/OX) signaling associated with exposure status. Two weeks after discontinuation of the alcohol vapor exposure and drinking during adolescence, rats were tested in adulthood for anxiety-like behaviors using a modified open-field conflict task, pre-pulse facilitation of startle response, light/dark box, and marble burying test. Adolescent alcohol exposure led to overall decreased startle response and increased behavioral arousal in the light/dark chamber during adulthood. Additionally, male rats demonstrated more disinhibited behavior during the conflict task compared to females, and female rats exhibited more rearing behavior during the light/dark test. Rats were also given a 2-bottle choice test that resulted in adolescent alcohol-exposed rats drinking significantly more alcohol in adulthood. Further, female rats also consumed more alcohol in adulthood compared to males. Estrous cycle phase did not account for any of the sex differences observed in the behavioral measures. Histological results indicated that adolescent alcohol did not alter Hcrt/OX-1 or Hcrt/OX-2 receptor mRNA expression levels in adult rats compared to control adults. However, female rats expressed a higher level of Hcrt/OX-1 and Hcrt/OX-2 receptor mRNA in the frontal cortex compared to males. These data suggest that our current model of intermittent ethanol exposure in adolescence can modestly affect both behavior and future consumption of alcohol and that Hcrt/OX receptor signaling differs between males and females.

Project description:BackgroundDual systems theories suggest that greater imbalance between higher reward sensitivity and lower cognitive control across adolescence conveys risk for behaviors such as heavy episodic drinking (HED). Prior research demonstrated that psychological analogues of these systems, sensation seeking and premeditation, change from childhood through emerging adulthood, and each has been independently linked with HED. However, few studies have assessed whether change over time in these developing analogues is prospectively associated with HED. Moreover, we know of no research that has shown whether within-person differences between higher sensation seeking and relatively lower premeditation across the adolescent period predict HED in emerging adulthood.MethodsProspective data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study (n = 715) were used to examine the association of sensation seeking and premeditation with HED among adolescents ages 16 to 20 years. We used novel applications of latent difference score modeling and growth curve analysis to test whether increasing sensation seeking, premeditation, and their imbalance over time are associated with HED across the study period, and whether these associations differed by sex.ResultsWhereas premeditation increased linearly from adolescence through emerging adulthood across sexes, males reported growth and females reported decline in sensation seeking. Sensation seeking in adolescence (and not premeditation) was associated with higher levels of HED by emerging adulthood. Importantly, greater imbalance between sensation seeking and premeditation was associated with higher levels of HED by emerging adulthood though we note that variability capturing this imbalance correlated highly (r = 0.86) with baseline levels of sensation seeking.ConclusionsDevelopmental imbalance between higher sensation seeking and lower premeditation in late adolescence may be a risk factor for greater HED in emerging adulthood.

Dataset Information

Chronic Drinking During Adolescence Predisposes the Adult Rat for Continued Heavy Drinking: Neurotrophin and Behavioral Adaptation after Long-Term, Continuous Ethanol Exposure.

Publications

Chronic Drinking During Adolescence Predisposes the Adult Rat for Continued Heavy Drinking: Neurotrophin and Behavioral Adaptation after Long-Term, Continuous Ethanol Exposure.

Similar Datasets

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