Adolescent and adult rats differ in the amnesic effects of acute ethanol in two hippocampus-dependent tasks: Trace and contextual fear conditioning

Behav Brain Res. 2016 Feb 1;298(Pt A):78-87. doi: 10.1016/j.bbr.2015.06.046. Epub 2015 Jul 17.

Abstract

Experience-produced deficits in trace conditioning and context conditioning have been useful tools for examining the role of the hippocampus in learning. It has also been suggested that learning in these tasks is especially vulnerable to neurotoxic effects of alcohol during key developmental periods such as adolescence. In five experiments we systematically examined the presence and source of age-dependent vulnerability to the memory-disrupting effects of acute ethanol in trace conditioning and contextual fear conditioning. In Experiment 1a pre-training ethanol disrupted trace conditioning more strongly in adolescent (postnatal day, PD30-35) than adult rats (PD65-75). In Experiment 1b when pre-training ethanol was accompanied by pre-test ethanol no deficit in trace conditioning was observed in adolescents, suggesting that state-dependent retrieval failure mediated ethanol's disruption of trace conditioning at this age. Experiment 2a and b examined the effect of ethanol pretreatment on context conditioning. Here, adult but not adolescent rats were impaired in conditioned freezing to context cues. Experiment 2c explored state-dependency of this effect. Pre-training ethanol continued to disrupt context conditioning in adults even when ethanol was also administered prior to test. Collectively these findings reveal clear age-dependent and task-dependent vulnerabilities in ethanol's disruptive effects on hippocampus-dependent memory. Adolescents were more disrupted by ethanol in trace conditioning than adults, and adults were more disrupted by ethanol in context conditioning than adolescents. We suggest that adolescents may be more susceptible to changes in internal state (state-dependent retrieval failure) than adults and that ethanol disrupted performance in trace and context conditioning through different mechanisms. Relevance of these findings to theories of hippocampus function is discussed.

Keywords: Adolescence; Alcohol; Context conditioning; Fear conditioning; Freezing; Hippocampus; Trace conditioning.

MeSH terms

  • Aging / drug effects*
  • Aging / physiology
  • Aging / psychology
  • Amnesia / chemically induced
  • Amnesia / physiopathology
  • Animals
  • Conditioning, Psychological / drug effects*
  • Conditioning, Psychological / physiology
  • Dose-Response Relationship, Drug
  • Ethanol / pharmacology*
  • Fear / drug effects*
  • Fear / physiology
  • Female
  • Freezing Reaction, Cataleptic / drug effects
  • Freezing Reaction, Cataleptic / physiology
  • Hippocampus / drug effects
  • Hippocampus / growth & development
  • Male
  • Memory / drug effects*
  • Memory / physiology
  • Neuropsychological Tests
  • Psychotropic Drugs / pharmacology*
  • Random Allocation
  • Rats, Sprague-Dawley
  • Sex Characteristics

Substances

  • Psychotropic Drugs
  • Ethanol