AMPA receptor and metabotropic glutamate receptor 1 adaptations in the nucleus accumbens core during incubation of methamphetamine craving

Murray, Conor H.; Loweth, Jessica A.; Milovanovic, Mike; Stefanik, Michael T.; Caccamise, Aaron; Dolubizno, Hubert; Funke, Jonathan R.; Wolf, Marina E.

doi:10.1038/s41386-019-0425-5

Cited by 30 publications

(57 citation statements)

References 46 publications

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“…Given the well-established role of AMPA receptors in synaptic plasticity ( Diering and Huganir, 2018 ), our results suggest a mechanism via which increased expression of AMPA receptors might enhance cue-induced oxycodone seeking because of strengthened synaptic connections in the hippocampus during long-term withdrawal from oxycodone. The proposition of the involvement of these receptors in oxycodone craving is also consistent with previous studies that had reported increased expression of AMPA receptors in the nucleus accumbens of rats had exhibited incubation of cocaine ( Conrad et al, 2008 ; Mameli et al, 2009 ; McCutcheon et al, 2011 ) or methamphetamine ( Scheyer et al, 2016 ; Murray et al, 2019 ) craving. It is important to note that although the relative changes in expression of GluA1 , GluA2 , and GluA3 were approximately the same in the LgA groups, there still might be distinct changes in receptor compositions that occur after translation and/or during assembly of these receptors that cannot be assessed by measuring only gene expression.…”

Section: Discussionsupporting

confidence: 90%

Prolonged Withdrawal From Escalated Oxycodone Is Associated With Increased Expression of Glutamate Receptors in the Rat Hippocampus

2021

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People suffering from opioid use disorder (OUD) exhibit cognitive dysfunctions. Here, we investigated potential changes in the expression of glutamate receptors in rat hippocampi at 2 h and 31 days after the last session of oxycodone self-administration (SA). RNA extracted from the hippocampus was used in quantitative polymerase chain reaction analyses. Rats, given long-access (9 h per day) to oxycodone (LgA), took significantly more drug than rats exposed to short-access (3 h per day) (ShA). In addition, LgA rats could be further divided into higher oxycodone taking (LgA-H) or lower oxycodone taking (LgA-L) groups, based on a cut-off of 50 infusions per day. LgA rats, but not ShA, rats exhibited incubation of oxycodone craving. In addition, LgA rats showed increased mRNA expression of GluA1-3 and GluN2a-c subunits as well as Grm3, Grm5, Grm6, and Grm8 subtypes of glutamate receptors after 31 days but not after 2 h of stopping the SA experiment. Changes in GluA1-3, Grm6, and Grm8 mRNA levels also correlated with increased lever pressing (incubation) after long periods of withdrawal from oxycodone. More studies are needed to elucidate the molecular mechanisms involved in altering the expression of these receptors during withdrawal from oxycodone and/or incubation of drug seeking.

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Section: Discussionsupporting

confidence: 90%

Prolonged Withdrawal From Escalated Oxycodone Is Associated With Increased Expression of Glutamate Receptors in the Rat Hippocampus

2021

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“…Given the wellestablished role of AMPA receptors in synaptic plasticity [Diering et al, 2018], our results suggest a mechanism via which increased expression of AMPA receptors might enhance cue-induced oxycodone seeking because of strengthened synaptic connections in the hippocampus during longterm withdrawal from oxycodone. The proposition of the involvement of these receptors in oxycodone craving is also consistent with previous studies that had reported increased expression of AMPA receptors in the nucleus accumbens of rats had exhibited incubation of cocaine [Conrad et al, 2008;Mameli et al, 2009;McCutcheon et al, 2011] or methamphetamine [Murray et al 2019;Scheyer et al, 2016] craving. It is important to note that although the relative changes in expression of GluA1, GluA2, and GluA3 were approximately the same in the LgA groups, there still might be distinct changes in receptor compositions that occur after translation and/or during assembly of these receptors that cannot be assessed by measuring only gene expression.…”

Section: Discussionsupporting

confidence: 90%

Prolonged Withdrawal from Escalated Oxycodone is Associated with Increased Expression of Glutamate Receptors in the Rat Hippocampus

Salisbury

Blackwood

Cadet

2020

Preprint

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People suffering from opioid use disorder (OUD) exhibit cognitive dysfunctions. Here, we investigated potential changes in the expression of glutamate receptors in rat hippocampi at 2 hours and 31 days after the last session of oxycodone self-administration (SA). RNA extracted from the hippocampus was used in quantitative polymerase chain reaction (qPCR) analyses. Rats, given long-access (9 hours per day) to oxycodone (LgA), took significantly more drug than rats exposed to short-access (3 hours per day) (ShA). In addition, LgA rats could be further divided into higher oxycodone taking (LgA-H) or lower oxycodone taking (LgA-L) groups, based on a cut-off of 50 infusions per day. LgA rats, but not ShA, rats exhibited incubation of oxycodone craving. In addition, LgA rats showed increased mRNA expression of GluA1-3 and GluN2a-c subunits as well as Grm3, Grm5, Grm6 and Grm8 subtypes of glutamate receptors after 31 days but not after 2 hours of stopping the SA experiment. Changes in GluA1-3, Grm6, and Grm8 mRNA levels also correlated with increased lever pressing (incubation) after long periods of withdrawal from oxycodone. More studies are needed to elucidate the molecular mechanisms involved in altering the expression of these receptors during withdrawal from oxycodone and/or incubation of drug seeking.

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“…Subsequent studies identified several neural mechanisms underlying this incubation, primarily focusing on cocaine 11 . Recent studies also investigated neural substrates involved in incubation of heroin 12–14 and methamphetamine craving 15–25 . However, only three recently published studies 26–28 began exploring neural mechanisms underlying incubation of oxycodone craving.…”

Section: Introductionmentioning

confidence: 99%

Role of orbitofrontal cortex in incubation of oxycodone craving in male rats

et al. 2020

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One of the main challenges in treating opioid‐use disorders is relapse during abstinence, triggered by re‐exposure to drug‐associated cues. Previous studies have demonstrated that drug‐seeking in rats progressively increases over time during withdrawal (incubation of drug craving). Here, we used male rats and examined neural mechanisms underlying incubation of craving to oxycodone, a commonly abused prescription opioid, and we focused on orbitofrontal cortex (OFC), a brain region previously implicated in incubation of heroin craving. We first used neuronal activity marker Fos and measured neuronal activation in OFC (ventral and lateral OFC) associated with day‐1 and day‐15 relapse tests. Next, we determined the effect of pharmacological reversible inactivation of OFC on incubated oxycodone seeking on withdrawal day 15. Finally, we determined the effect of reversible inactivation of OFC on nonincubated oxycodone seeking on withdrawal day 1. We found that lever presses during relapse tests were higher on withdrawal day 15 than on withdrawal day 1 (incubation of oxycodone craving). Incubation of oxycodone craving is accompanied with a time‐dependent increase of Fos protein expression in both ventral and lateral OFC. Lastly, OFC inactivation decreased oxycodone seeking on withdrawal day 15 but had no effect on withdrawal day 1. Together with the previous heroin study, results here show that OFC plays a critical role in incubation of opioid craving.

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AMPA receptor and metabotropic glutamate receptor 1 adaptations in the nucleus accumbens core during incubation of methamphetamine craving

Cited by 30 publications

References 46 publications

Prolonged Withdrawal From Escalated Oxycodone Is Associated With Increased Expression of Glutamate Receptors in the Rat Hippocampus

Prolonged Withdrawal From Escalated Oxycodone Is Associated With Increased Expression of Glutamate Receptors in the Rat Hippocampus

Prolonged Withdrawal from Escalated Oxycodone is Associated with Increased Expression of Glutamate Receptors in the Rat Hippocampus

Role of orbitofrontal cortex in incubation of oxycodone craving in male rats

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