Author ORCID Identifier

https://orcid.org/0000-0001-8913-079X

Date Available

4-28-2024

Year of Publication

2023

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Arts and Sciences

Department/School/Program

Psychology

First Advisor

Dr. Mark A. Prendergast

Abstract

Fetal alcohol spectrum disorders (FASDs) are a set of cognitive and behavioral abnormalities that arise in ~5% of children who have been prenatally-exposed to alcohol. Prenatal alcohol exposure (PAE) can cause impairments in learning acquisition, working memory, response inhibition, and attentional-set shifting that result in exaggerated deficits in executive function and impairments in goal-seeking behavior. There are standard procedures used in rodent research to address some components of these deficits, but few procedures are sensitive enough to comprehensively assess such deficits. To address this issue in FASDs research techniques, we developed a procedure that requires prolonged executive function in a sequential discrimination task mapped onto the T-maze apparatus. Rats were prenatally-exposed to intragastric 4g/kg/day ethanol between gestational day 14-20 and performed the discrimination task in one session between post-natal day 35-38. Sixty-grit sandpaper was matched by dimensions and color to fit the T-maze arm. The sandpaper insert was made to randomly alternate between left and right arm throughout all discriminations. Rats were assigned to 1 of 2 dimensional conditions: Spatial-to-Tactile or Tactile-to-Spatial. Serial discrimination for rats in Spatial-to-Tactile were: Left-Turn, Right-Turn, Sandpaper-Floor, Smooth-Floor. Serial discrimination for rats in Tactile-to-Spatial were: Sandpaper-Floor, Smooth-Floor, Left-Turn, Right-Turn. Regardless of dimensional condition, the 4 serial discriminations were: 1) simple discrimination (SD), 2) intradimensional shift (ID), 3) extradimensional shift (ED), and 4) extradimensional reversal (EDREV). Rats were reinforced with ¼ Cheerio and proceeded to subsequent discrimination stages after a) 6 consecutive correct discriminations or b) exceeding naïve-derived cutoff. Analysis was conducted for SD, ID, ED, and EDREV at the level of (+/-) PAE, dimensional condition, and sex; additionally, analyses were conducted for SD vs. ID, ID vs. ED, and ED vs. EDREV at the level of (+/-) PAE, dimensional condition, and sex. Broadly, PAE rats performed worse than typical rats. Specifically, PAE rats performed worse in all analyses except for the discrete analysis of ED performance as well as the analysis of SD vs. ID. In some cases, sex and dimensional condition interacted with the effect of PAE. This paradigm may be more sensitive to detect nuanced impairments in FASDs rodent models than other simpler paradigms. Further consideration of different maternal alcohol exposure periods, offspring sex differences, and neurological correlates could bolster this paradigm and improve translatability to humans. Improving rodent FASDs models could help our understanding of FASDs diagnostic peculiarities and provide specialized therapeutic targets to children suffering from prenatal alcohol exposure.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2023.096

Funding Information

This study was supported by pilot funds from the University of Kentucky’s Substance Use Priority Research Area (SUPRA), supported by the Vice President for Research in from 2021-2022.

This study was supported by the National Institute on Alcohol Abuse and Alcoholism training grant T32 AA027488 from 2021-2023.

This study was supported by the Lipman Research Fund for the Prevention of Drug and Alcohol Abuse from 2022-2023.

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