國立虎尾科技大學 |

The Enduring Consequences of Prenatal Opioid Exposure.

紀錄類型:	書目-語言資料,手稿 : Monograph/item
正題名/作者:	The Enduring Consequences of Prenatal Opioid Exposure./
作者:	Grecco, Gregory Giovanni.
面頁冊數:	1 online resource (229 pages)
附註:	Source: Dissertations Abstracts International, Volume: 83-09, Section: B.
Contained By:	Dissertations Abstracts International83-09B.
標題:	Neurosciences. -
電子資源:	click for full text (PQDT)
ISBN:	9798209877592

The Enduring Consequences of Prenatal Opioid Exposure.
Grecco, Gregory Giovanni.

The Enduring Consequences of Prenatal Opioid Exposure. - 1 online resource (229 pages)

Source: Dissertations Abstracts International, Volume: 83-09, Section: B.

Thesis (Ph.D.)--Indiana University - Purdue University Indianapolis, 2022.

Includes bibliographical references

The opioid crisis has resulted in an unprecedented number of neonates born with prenatal opioid exposure; however, the long-term effects of opioid exposure on offspring behavior and neurodevelopment remain relatively unknown. I developed a translational mouse model of prenatal methadone exposure (PME) that resembles the typical pattern of opioid use by pregnant women who first use oxycodone then switch to methadone maintenance pharmacotherapy, and subsequently become pregnant while maintained on methadone. PME produced substantial impairments in offspring growth, sensorimotor milestone acquisition, and activity in an open field. Furthermore, these behavioral alterations were associated with significant disruptions in the primary motor cortex (M1). Notably, layer 5 pyramidal neurons of the M1 displayed significantly increased voltage sag which is primarily mediated by HCN1 channels. Interestingly, the α2-adrenergic receptor, a known modulator of HCN1 channels, displayed significantly increased expression in the M1 of PME animals. The locomotor activity in an open field was significantly reduced following in vivo pharmacological activation of the α2-adrenergic receptor with clonidine in PME offspring suggesting this may be therapeutic target for the hyperactivity associated with prenatal exposure to opioids. Previous work has also described an association between prenatal opioid exposure and alterations in opioid reward-related behavior; however, the effect of PME on alcohol reward remains undetermined. Given the widespread accessibility and usage, alcohol represents the most likely addictive substance the growing population of opioid exposed neonates will encounter as they age. I discovered that PME disrupts conditioned preference for alcohol, enhances the locomotor stimulating effects of alcohol, and increases alcohol consumption in a sex-dependent manner. This alcohol-reward phenotype in PME offspring was associated with altered excitatory neurotransmission and disrupted cannabinoid-mediated long-term depression (CB-LTD) in the dorsolateral striatum, an important substrate involved in compulsive drug use. Further work is required to determine the specific inputs at which CB-LTD is disrupted and if restoring this form of plasticity in PME animals prevents the enhanced alcohol addiction phenotype.

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

Mode of access: World Wide Web

ISBN: 9798209877592Subjects--Topical Terms:

593561
Neurosciences.
Subjects--Index Terms:

AddictionIndex Terms--Genre/Form:

554714
Electronic books.

The Enduring Consequences of Prenatal Opioid Exposure.
LDR:03647ntm a22003737 4500 001 1147945
005 20240916065945.5
006 m o d
007 cr bn ---uuuuu
008 250605s2022 xx obm 000 0 eng d
020 $a 9798209877592
035 $a (MiAaPQ)AAI28963380
035 $a AAI28963380
040 $a MiAaPQ $b eng $c MiAaPQ $d NTU
100 1 $a Grecco, Gregory Giovanni. $3 1473798
245 1 4 $a The Enduring Consequences of Prenatal Opioid Exposure.
264 0 $c 2022
300 $a 1 online resource (229 pages)
336 $a text $b txt $2 rdacontent
337 $a computer $b c $2 rdamedia
338 $a online resource $b cr $2 rdacarrier
500 $a Source: Dissertations Abstracts International, Volume: 83-09, Section: B.
500 $a Advisor: Sheets, Patrick.
502 $a Thesis (Ph.D.)--Indiana University - Purdue University Indianapolis, 2022.
504 $a Includes bibliographical references
520 $a The opioid crisis has resulted in an unprecedented number of neonates born with prenatal opioid exposure; however, the long-term effects of opioid exposure on offspring behavior and neurodevelopment remain relatively unknown. I developed a translational mouse model of prenatal methadone exposure (PME) that resembles the typical pattern of opioid use by pregnant women who first use oxycodone then switch to methadone maintenance pharmacotherapy, and subsequently become pregnant while maintained on methadone. PME produced substantial impairments in offspring growth, sensorimotor milestone acquisition, and activity in an open field. Furthermore, these behavioral alterations were associated with significant disruptions in the primary motor cortex (M1). Notably, layer 5 pyramidal neurons of the M1 displayed significantly increased voltage sag which is primarily mediated by HCN1 channels. Interestingly, the α2-adrenergic receptor, a known modulator of HCN1 channels, displayed significantly increased expression in the M1 of PME animals. The locomotor activity in an open field was significantly reduced following in vivo pharmacological activation of the α2-adrenergic receptor with clonidine in PME offspring suggesting this may be therapeutic target for the hyperactivity associated with prenatal exposure to opioids. Previous work has also described an association between prenatal opioid exposure and alterations in opioid reward-related behavior; however, the effect of PME on alcohol reward remains undetermined. Given the widespread accessibility and usage, alcohol represents the most likely addictive substance the growing population of opioid exposed neonates will encounter as they age. I discovered that PME disrupts conditioned preference for alcohol, enhances the locomotor stimulating effects of alcohol, and increases alcohol consumption in a sex-dependent manner. This alcohol-reward phenotype in PME offspring was associated with altered excitatory neurotransmission and disrupted cannabinoid-mediated long-term depression (CB-LTD) in the dorsolateral striatum, an important substrate involved in compulsive drug use. Further work is required to determine the specific inputs at which CB-LTD is disrupted and if restoring this form of plasticity in PME animals prevents the enhanced alcohol addiction phenotype.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2024
538 $a Mode of access: World Wide Web
650 4 $a Neurosciences. $3 593561
653 $a Addiction
653 $a Methadone
653 $a Neurodevelopment
653 $a Opioid
653 $a Prenatal
655 7 $a Electronic books. $2 local $3 554714
690 $a 0317
710 2 $a ProQuest Information and Learning Co. $3 1178819
710 2 $a Indiana University - Purdue University Indianapolis. $b Medical Neuroscience. $3 1473799
773 0 $t Dissertations Abstracts International $g 83-09B.
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28963380 $z click for full text (PQDT)