Adolescent intermittent ethanol exposure is associated with increased risky choice and decreased dopaminergic and cholinergic neuron markers in adult rats

Int J Neuropsychopharmacol. 2014 Oct 31;18(2):pyu003. doi: 10.1093/ijnp/pyu003.

Abstract

Background: Binge drinking is prevalent during adolescence and may have effects on the adult brain and behavior. The present study investigated whether adolescent intermittent ethanol exposure alters adult risky choice and prefrontal dopaminergic and forebrain cholinergic neuronal marker levels in male Wistar rats.

Methods: Adolescent (postnatal day 28-53) rats were administered 5 g/kg of 25% (vol/vol) ethanol 3 times/d in a 2-days-on/2-days-off exposure pattern. In adulthood, risky choice was assessed in the probability discounting task with descending and ascending series of large reward probabilities and after acute ethanol challenge. Immunohistochemical analyses assessed tyrosine hydroxylase, a marker of dopamine and norepinephrine in the prelimbic and infralimbic cortices, and choline acetyltransferase, a marker of cholinergic neurons, in the basal forebrain.

Results: All of the rats preferred the large reward when it was delivered with high probability. When the large reward became unlikely, control rats preferred the smaller, safe reward, whereas adolescent intermittent ethanol-exposed rats continued to prefer the risky alternative. Acute ethanol had no effect on risky choice in either group of rats. Tyrosine hydroxylase (prelimbic cortex only) and choline acetyltransferase immunoreactivity levels were decreased in adolescent intermittent ethanol-exposed rats compared with controls. Risky choice was negatively correlated with choline acetyltransferase, implicating decreased forebrain cholinergic activity in risky choice.

Conclusions: The decreases in tyrosine hydroxylase and choline acetyltransferase immunoreactivity suggest that adolescent intermittent ethanol exposure has enduring neural effects that may lead to altered adult behaviors, such as increased risky decision making. In humans, increased risky decision making could lead to maladaptive, potentially harmful consequences.

Keywords: adolescence; cholinergic neurons; dopaminergic neurons; ethanol; probability discounting.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Area Under Curve
  • Basal Forebrain / drug effects
  • Basal Forebrain / growth & development
  • Basal Forebrain / physiopathology
  • Binge Drinking / physiopathology
  • Cell Count
  • Central Nervous System Depressants / administration & dosage
  • Central Nervous System Depressants / adverse effects*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / growth & development
  • Cerebral Cortex / physiopathology
  • Choice Behavior / drug effects*
  • Choice Behavior / physiology
  • Choline O-Acetyltransferase / metabolism
  • Cholinergic Neurons / drug effects*
  • Cholinergic Neurons / physiology
  • Dopaminergic Neurons / drug effects*
  • Dopaminergic Neurons / physiology
  • Ethanol / administration & dosage
  • Ethanol / adverse effects*
  • Immunohistochemistry
  • Male
  • Neuropsychological Tests
  • Probability
  • Rats, Wistar
  • Reward
  • Risk-Taking*
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Central Nervous System Depressants
  • Ethanol
  • Tyrosine 3-Monooxygenase
  • Choline O-Acetyltransferase