Adolescent oxycodone exposure inhibits withdrawal-induced expression of genes associated with the dopamine transmission.
Adolescent oxycodone exposure inhibits withdrawal-induced expression of genes associated with the dopamine transmission.
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DOI：
10.1111/adb.12994
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发表时间：
2021-07
影响因子：
3.4
通讯作者：
Blendy JA
中科院分区：
文献类型：
--
作者：
Carpenter MD;Manners MT;Heller EA;Blendy JA
Prescription opioid misuse is a major public health concern among children and adolescents in the USA . Opioids are the most commonly abused drugs and are the fastest growing drug problem among adolescents . In humans and animals, adolescence is a particularly sensitive period associated with an increased response to drugs of abuse . Our previous studies indicate that oxycodone exposure during adolescence increases morphine reward in adulthood . How early drug exposure mediates long-term changes in the brain and behavior is not known, but epigenetic regulation is a likely mechanism. To address this question, we exposed mice to oxycodone or saline during adolescence and examined epigenetic modifications at genes associated with dopamine activity during adulthood at early and late withdrawal, in the ventral tegmental area (VTA). We then compared these to alterations in the VTA of adult-treated mice following an equivalent duration of exposure and withdrawal to determine if the effects of oxycodone are age-dependent. We observed persistence of adolescent-like gene expression following adolescent oxycodone exposure relative to age-matched saline exposed controls, although dopamine related gene expression was transiently activated at 1-day of withdrawal. Following prolonged withdrawal enrichment of the repressive histone mark, H3K27me3, was maintained, consistent with inhibition of gene regulation following adolescent exposure. In contrast, mice exposed to oxycodone as adults showed loss of the repressive mark and increased gene expression following 28-days of withdrawal following oxycodone exposure. Together our findings provide evidence that adolescent oxycodone exposure has long-term epigenetic consequences in VTA of the developing brain.
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影响因子：
5.1
作者：
Cerda, Magdalena;Santaella, Julian;Martins, Silvia S.
通讯作者：
Martins, Silvia S.
DOI：
10.1016/j.ijdevneu.2009.08.009
发表时间：
2009-12-01
影响因子：
1.8
作者：
Philpot, Rex M.;Wecker, Lynn;Kirstein, Cheryl L.
通讯作者：
Kirstein, Cheryl L.
影响因子：
3.3
作者：
Morrison KE;Rodgers AB;Morgan CP;Bale TL
通讯作者：
Bale TL
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
16.6
作者：
Carpenter, Marco D.;Hu, Qiwen;Heller, Elizabeth A.
通讯作者：
Heller, Elizabeth A.