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Adult Hippocampal Dysfunction and Related Cognitive Impairments Following Prenatal Methadone Exposure.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Adult Hippocampal Dysfunction and Related Cognitive Impairments Following Prenatal Methadone Exposure./
Author:	Gamble, Meredith Erin.
Description:	1 online resource (161 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 84-12, Section: B.
Contained By:	Dissertations Abstracts International84-12B.
Subject:	Neurosciences. -
Online resource:	click for full text (PQDT)
ISBN:	9798379733582

Adult Hippocampal Dysfunction and Related Cognitive Impairments Following Prenatal Methadone Exposure.
Gamble, Meredith Erin.

Adult Hippocampal Dysfunction and Related Cognitive Impairments Following Prenatal Methadone Exposure. - 1 online resource (161 pages)

Source: Dissertations Abstracts International, Volume: 84-12, Section: B.

Thesis (Ph.D.)--State University of New York at Binghamton, 2023.

Includes bibliographical references

Prenatal opioid exposures lead to extensive cognitive, motor, and emotion-regulation impairments in children, persisting at least through early school-age. These findings include deficits resulting from prenatal exposure to methadone, an opioid pharmacotherapy that is typically used in the treatment of opioid use disorder, even during pregnancy. Preclinical studies in young rodents have observed similar deficits in learning and memory tasks resulting from prenatal opioid exposures, including methadone. However, there is limited research examining whether these impairments persist throughout the lifetime and if any additional cognitive consequences emerge later in life. The current studies aim to examine the persistent nature of cognitive deficits resulting from prenatal methadone exposure (PME) in adult male and female rats. Here, we also begin exploring one brain region that may be disrupted following PME, and ultimately contributing to learning and memory impairments, the dentate gyrus of the hippocampus. Pregnant Sprague Dawley rats received subcutaneous methadone or water injections twice daily from gestational days 3 - 20 or were left undisturbed as naive controls. Adult male and female offspring were tested on several hippocampal-dependent learning and memory tasks to evaluate spatial, working, and recognition learning and memory, as well as contextual fear conditioning and pattern separation. Additionally, hippocampal dentate granule cell function was assessed using whole-cell patch-clamp electrophysiology, and disruptions in adult hippocampal neurogenesis were evaluated using BrdU labeling for proliferation and survival of adult-born neurons. Results indicate significant behavioral impairments, including altered recognition memory in both sexes, and impaired working spatial memory and heightened fear response in females. We have also found increased inhibition of adult female hippocampal dentate granule cells and reduced adult-born dentate granule cell survival in both sexes. This work supports the continued investigation of methadone exposures during pregnancy and how PME may impair the behavioral and neural function of offspring throughout their lifetime. With these findings, we hope to contribute to the current knowledge of how this pharmacotherapy may alter the neural developmental trajectory of exposed individuals, and we hope this information will eventually help to prepare for and treat these exposed individuals to promote a better quality of life, long-term.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2024

Mode of access: World Wide Web

ISBN: 9798379733582Subjects--Topical Terms:

593561
Neurosciences.
Subjects--Index Terms:

HippocampusIndex Terms--Genre/Form:

554714
Electronic books.

Adult Hippocampal Dysfunction and Related Cognitive Impairments Following Prenatal Methadone Exposure.
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520 $a Prenatal opioid exposures lead to extensive cognitive, motor, and emotion-regulation impairments in children, persisting at least through early school-age. These findings include deficits resulting from prenatal exposure to methadone, an opioid pharmacotherapy that is typically used in the treatment of opioid use disorder, even during pregnancy. Preclinical studies in young rodents have observed similar deficits in learning and memory tasks resulting from prenatal opioid exposures, including methadone. However, there is limited research examining whether these impairments persist throughout the lifetime and if any additional cognitive consequences emerge later in life. The current studies aim to examine the persistent nature of cognitive deficits resulting from prenatal methadone exposure (PME) in adult male and female rats. Here, we also begin exploring one brain region that may be disrupted following PME, and ultimately contributing to learning and memory impairments, the dentate gyrus of the hippocampus. Pregnant Sprague Dawley rats received subcutaneous methadone or water injections twice daily from gestational days 3 - 20 or were left undisturbed as naive controls. Adult male and female offspring were tested on several hippocampal-dependent learning and memory tasks to evaluate spatial, working, and recognition learning and memory, as well as contextual fear conditioning and pattern separation. Additionally, hippocampal dentate granule cell function was assessed using whole-cell patch-clamp electrophysiology, and disruptions in adult hippocampal neurogenesis were evaluated using BrdU labeling for proliferation and survival of adult-born neurons. Results indicate significant behavioral impairments, including altered recognition memory in both sexes, and impaired working spatial memory and heightened fear response in females. We have also found increased inhibition of adult female hippocampal dentate granule cells and reduced adult-born dentate granule cell survival in both sexes. This work supports the continued investigation of methadone exposures during pregnancy and how PME may impair the behavioral and neural function of offspring throughout their lifetime. With these findings, we hope to contribute to the current knowledge of how this pharmacotherapy may alter the neural developmental trajectory of exposed individuals, and we hope this information will eventually help to prepare for and treat these exposed individuals to promote a better quality of life, long-term.
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