Pharmacokinetic and pharmacodynamic considerations in developing a response to the opioid epidemic

Balyan, Rajiv; Hahn, David; Huang, Henry; Chidambaran, Vidya

doi:10.1080/17425255.2020.1721458

Cited by 12 publications

(18 citation statements)

References 143 publications

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“…S1). Importantly, pPKC/PKC ratios were significantly increased [F (3,18) = 4.45, p = 0.0165] in the LgA-H group compared to the other groups (Supplementary Fig. S1).…”

Section: Effects Of Early Withdrawal and Oxycodone Sa On The Activation Of Pkcmentioning

confidence: 99%

“…The opioid epidemic remains a public health crisis 1,2 . This is related, in part, to the over-prescription of the opioid agonist, oxycodone, for pain management [3][4][5][6] . Its illicit abuse has also contributed to the high number of overdose-related deaths 7,8 .…”

mentioning

confidence: 99%

“…Pharmacological approaches to treat opioid use disorders (OUDs) have mainly included the use of agents that interact with opioids receptors 3,12,13 . Upon activation, opioid receptors transmit signals to the nucleus via intracellular events that involve modulation of some kinase cascades [14][15][16] , with consequent changes in gene expression 17,18 .…”

mentioning

confidence: 99%

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Oxycodone self-administration activates the mitogen-activated protein kinase/ mitogen- and stress-activated protein kinase (MAPK-MSK) signaling pathway in the rat dorsal striatum

Blackwood¹,

McCoy²,

Ladenheim³

et al. 2021

Sci Rep

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To identify signaling pathways activated by oxycodone self-administration (SA), Sprague–Dawley rats self-administered oxycodone for 20 days using short—(ShA, 3 h) and long-access (LgA, 9 h) paradigms. Animals were euthanized 2 h after SA cessation and dorsal striata were used in post-mortem molecular analyses. LgA rats escalated their oxycodone intake and separated into lower (LgA-L) or higher (LgA-H) oxycodone takers. LgA-H rats showed increased striatal protein phosphorylation of ERK1/2 and MSK1/2. Histone H3, phosphorylated at serine 10 and acetylated at lysine 14 (H3S10pK14Ac), a MSK1/2 target, showed increased abundance only in LgA-H rats. RT-qPCR analyses revealed increased AMPA receptor subunits, GluA2 and GluA3 mRNAs, in the LgA-H rats. GluA3, but not GluA2, mRNA expression correlated positively with changes in pMSK1/2 and H3S10pK14Ac. These findings suggest that escalated oxycodone SA results in MSK1/2-dependent histone phosphorylation and increases in striatal gene expression. These observations offer potential avenues for interventions against oxycodone addiction.

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“…S1). Importantly, pPKC/PKC ratios were significantly increased [F (3,18) = 4.45, p = 0.0165] in the LgA-H group compared to the other groups (Supplementary Fig. S1).…”

Section: Effects Of Early Withdrawal and Oxycodone Sa On The Activation Of Pkcmentioning

confidence: 99%

mentioning

confidence: 99%

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Oxycodone self-administration activates the mitogen-activated protein kinase/ mitogen- and stress-activated protein kinase (MAPK-MSK) signaling pathway in the rat dorsal striatum

Blackwood¹,

McCoy²,

Ladenheim³

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The opioid epidemic remains a public health crisis 1,2 . This is related, in part, to the over-prescription of the opioid agonist, oxycodone, for pain management 3–6 . Its illicit abuse has also contributed to the high number of overdose-related deaths 7,8 .…”

Section: Introductionmentioning

confidence: 99%

“…Pharmacological approaches to treat opioid use disorders (OUDs) have mainly included the use of agents that interact with opioids receptors 3,12,13 . Upon activation, opioid receptors transmit signals to the nucleus via intracellular events that involve modulation of some kinase cascades 14–16 , with consequent changes in gene expression 17,18 .…”

Section: Introductionmentioning

confidence: 99%

Oxycodone self-administration activates the mitogen-activated protein kinase/mitogen- and stress-activated protein kinase (MAPK-MSK) signaling pathway in the rat dorsal striatum

Blackwood

McCoy

Ladenheim

et al. 2020

Preprint

View full text Add to dashboard Cite

To identify signaling pathways activated by oxycodone self-administration (SA), Sprague-Dawley rats self-administered oxycodone for 20 days using short-access (ShA, 3 h) and long-access (LgA, 9 h) paradigms. Animals were euthanized two hours after SA cessation and dorsal striata were used in post-mortem molecular analyses. LgA rats escalated their oxycodone intake and separated into lower (LgA-L) or higher (LgA-H) oxycodone takers. LgA-H rats showed increased striatal protein phosphorylation of ERK1/2 and MSK1/2. Histone H3, phosphorylated at serine 10 and acetylated at lysine 14 (H3S10pK14Ac), a MSK1/2 target, showed increased abundance only in LgA-H rats. RT-qPCR analyses revealed increased AMPA receptor subunits, GluA2 and GluA3 mRNAs in the LgA-H rats. GluA3, but not GluA2, expression correlated positively with changes in pMSK1/2 and H3S10pK14Ac. Our findings indicate that escalated oxycodone SA results in MSK1/2-dependent histone phosphorylation, which promoted increases in striatal gene expression. Our observations offer novel avenues for pharmacological interventions against oxycodone addiction.

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An Overview of Personalized Medicine Development Through Recent Advances in Genome-Wide Association Studies

Omerkić,

Ašić

2024

IFMBE Proceedings

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Pharmacokinetic and pharmacodynamic considerations in developing a response to the opioid epidemic

Cited by 12 publications

References 143 publications

Oxycodone self-administration activates the mitogen-activated protein kinase/ mitogen- and stress-activated protein kinase (MAPK-MSK) signaling pathway in the rat dorsal striatum

Oxycodone self-administration activates the mitogen-activated protein kinase/ mitogen- and stress-activated protein kinase (MAPK-MSK) signaling pathway in the rat dorsal striatum

Oxycodone self-administration activates the mitogen-activated protein kinase/mitogen- and stress-activated protein kinase (MAPK-MSK) signaling pathway in the rat dorsal striatum

An Overview of Personalized Medicine Development Through Recent Advances in Genome-Wide Association Studies

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