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bioRxiv · 10.1101/2024.03.06.583121

Maternal Alcohol Drinking Patterns Predict Offspring Neurobehavioral Outcomes

Myrick, A. R.·Jimenez, D.·Jacquez, B.·Noor, S.·Sun, M. S.·Milligan, E. D.·Valenzuela, C. F.·Linsenbardt, D.
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Abstract

SIGNIFICANCEThe timing, rate, and quantity of gestational alcohol consumption, collectively referred to here as Maternal Drinking Patterns (MDPs), are of known importance to fetal developmental outcomes. Though studies in rodents exist that have investigated the impact of gestational alcohol drinking characteristics, few have sought to determine the impact of MDPs on offspring behavioral outcomes. METHODSWe first used specialized equipment to record the precise amount and timing of binge alcohol consumption in pregnant mouse dams, and then characterized MDPs using Principle Component Analysis (PCA). We focused these analyses on the first fifteen minutes of every gestational drinking session when dams consumed the majority of each sessions alcohol (a phenomenon known as front-loading), as well as the entire 2 hour session across all days of gestation. We next tested offspring in open field and rotarod assays and evaluated these behavioral results in the context of MDPs. RESULTSMale alcohol exposed mice exhibited longer latencies to fall on the rotarod compared to their controls, which we attribute to a delayed decrease in body weight-gain not observed in females. This effect was found to be associated with MDPs within the first fifteen minutes of drinking, but not other MDPs. Female alcohol exposed mice had significantly reduced total locomotor activity in the open field compared to controls, and this effect was also associated with MDPs but only of the entire drinking session. Surprisingly, total gestational alcohol consumption alone was not associated with any particular behavioral outcome. Furthermore, we replicated robust behavioral data demonstrating development of allodynia in alcohol exposed mice where it did not develop in controls. CONCLUSIONSTo our knowledge, this report represents the highest resolution assessment of alcohol drinking throughout gestation, and one of few to have identified relationships between specific alcohol MDPs and neurobehavioral outcomes in offspring. Specifically, based on characteristics of the PCA groups, we found evidence that the rate of alcohol front-loading leads to developmental delays in males, whereas an interaction of front-loading rate and duration, overall persistence, and total amount consumed lead to a female-only decrease in locomotor activity. Beyond these results, we provide a method for precise and accessible tracking of such data.

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Myrick, A. R., Jimenez, D., Jacquez, B., Noor, S., Sun, M. S., Milligan, E. D., Valenzuela, C. F., Linsenbardt, D.. 2024-03-11. Maternal Alcohol Drinking Patterns Predict Offspring Neurobehavioral Outcomes. https://doi.org/10.1101/2024.03.06.583121

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