4.2 Article

Rehabilitation Training Using Complex Motor Learning Rescues Deficits in Eyeblink Classical Conditioning in Female Rats Induced by Binge-Like Neonatal Alcohol Exposure

期刊

ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
卷 37, 期 9, 页码 1561-1570

出版社

WILEY
DOI: 10.1111/acer.12122

关键词

Cerebellum; Ethanol; Eyeblink Conditioning; Fetal Alcohol Spectrum Disorder

资金

  1. [AA09838]
  2. [AA07462]
  3. NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P20GM103653] Funding Source: NIH RePORTER
  4. NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [R01AA009838, T32AA007462] Funding Source: NIH RePORTER

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Background Effective treatments for the behavioral and cognitive deficits in children with fetal alcohol spectrum disorders (FASD) are lacking, and translational approaches using animal models can help develop rational interventions. One such model, binge-like alcohol exposure in neonatal rats during the period of brain development comparable with that of the human third trimester, causes structural and functional damage to the cerebellum and disrupts cerebellar-dependent eyeblink classical conditioning. The eyeblink conditioning deficits first demonstrated in this rat model predicted the similar deficits subsequently demonstrated in children with FASD. Methods The current study extends this translational approach by testing the hypothesis that rehabilitation training involving 20days of training on traversal of an obstacle course (complex motor learning) would ameliorate the deficits on classical conditioning of eyeblink responses produced by the neonatal alcohol exposure. We have previously shown that this training stimulates cerebellar synaptic plasticity and improves alcohol-induced deficits on motor coordination tasks. Results The current studies found that rehabilitation training significantly attenuated alcohol-induced deficits in acquisition of eyeblink conditioning in females but not in males. These results are consistent with normalization of cerebellar-dependent learning, at least in alcohol-exposed females. Conclusions These findings extend previous studies in this model suggesting that rehabilitation of adolescents with FASD using training with complex motor learning tasks could be effective in ameliorating functional impairments associated with cerebellar damage. Eyeblink classical conditioning deficits are now well documented in children with FASD and could serve as an evaluation measure to continue to develop therapeutic interventions such as complex motor learning.

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