Withdrawal from repeated morphine administration augments expression of the RhoA network in the nucleus accumbens to control synaptic structure

Cahill, Michael E.; Browne, Caleb J.; Wang, Junshi; Hamilton, Peter J.; Dong, Yan; Nestler, Eric J.

doi:10.1111/jnc.14563

Cited by 18 publications

(14 citation statements)

References 43 publications

(117 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The morphological changes identified in this report are entirely consistent with these changes in gene translation. Morphine withdrawal is also associated with reduced dendritic spine density and synaptic reorganization in the striatum 46,47 . Since it is becoming increasingly clear that microglia participate in spine plasticity, we believe that these translational gene networks in microglia may be involved in this phenomenon.…”

Section: Striatal Microglia Morphology Is Altered By Morphine Toleranmentioning

confidence: 99%

RiboTag-Seq Reveals a Compensatory cAMP Responsive Gene Network in Striatal Microglia Induced by Morphine Withdrawal

Coffey

Lesiak

Marx

et al. 2020

Preprint

View full text Add to dashboard Cite

Microglia have recently been implicated in dependence to opioids. To investigate this directly, we used RNA sequencing of ribosome associated RNAs from striatal microglia (RiboTag-Seq) after the induction of morphine tolerance and then the precipitation of withdrawal by naloxone. We detected large, inverse changes in RNA translation following opioid tolerance and withdrawal, and bioinformatics analysis revealed an intriguing upregulation of cAMP-associated genes that are involved in microglial motility, morphology, and interactions with neurons. Three-dimensional histological reconstruction of microglia revealed changes in process branching and termination following opioid tolerance that were rapidly reversed during withdrawal and were consistent with cAMP effects on microglia morphology. Direct activation of Gicoupled DREADD receptors in microglia, rather than mimicking the effects of morphine, exacerbated opioid withdrawal. Together these indicate that microglial response to cAMP signaling can mitigate the rapid manifestations of opioid withdrawal. inverse relationship between gene expression changes duringFigure 4. Differential Expression Analysis | Naloxone administration to non-morphine-dependent animals has little effect on gene expression in the a, IP samples or d, Input samples. Morphine tolerance produces roughly equal numbers of upregulated and downregulated DEGs in both the b, IP sample and e, Input sample. Naloxone administration to morphine dependent animals produces mainly upregulation of DEGs in both the c, IP and f, Input samples. Gene expression changes during withdrawal are inversely correlated to gene expression changes during morphine tolerance in both the g, IP sample and h, Input sample.Roughly half of IP DEGs were also differentially expressed in the Input samples for both i, morphine tolerance and j, withdrawal, suggesting a common mechanism of action in neurons and microglia.

show abstract

Section: Striatal Microglia Morphology Is Altered By Morphine Toleranmentioning

confidence: 99%

RiboTag-Seq Reveals a Compensatory cAMP Responsive Gene Network in Striatal Microglia Induced by Morphine Withdrawal

Coffey

Lesiak

Marx

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Numerous brain regions are sensitive to both drugs and stress, including the nucleus accumbens (NAc) ( Hollon et al, 2015 ; Newman et al, 2018 ; Calarco and Lobo, 2020 ). Indeed, both chronic stress and opioid exposure cause structural changes in the NAc that are thought to drive stress-susceptibility or increased drug intake ( Matsubara et al, 1999 ; Robinson et al, 2002 ; Spiga et al, 2005 ; Diana et al, 2006 ; Christoffel et al, 2011a , b ; Golden et al, 2013 ; Pal and Das, 2013 ; Graziane et al, 2016 ; Guegan et al, 2016 ; Kobrin et al, 2016 ; Francis et al, 2017 ; Cahill et al, 2018 ; Geoffroy et al, 2019 ; Fox et al, 2020a , b ). These structural changes are primarily driven by Rho GTPases, and we and others have shown opioid withdrawal ( Cahill et al, 2018 ) and CSDS ( Francis et al, 2017 ; Fox et al, 2020a ) engage and alter NAc RhoA signaling.…”

Section: Introductionmentioning

confidence: 99%

Chronic Physical and Vicarious Psychosocial Stress Alter Fentanyl Consumption and Nucleus Accumbens Rho GTPases in Male and Female C57BL/6 Mice

Franco

Wulff

Lobo

et al. 2022

Front. Behav. Neurosci.

View full text Add to dashboard Cite

Chronic stress can increase the risk of developing a substance use disorder in vulnerable individuals. Numerous models have been developed to probe the underlying neurobiological mechanisms, however, most prior work has been restricted to male rodents, conducted only in rats, or introduces physical injury that can complicate opioid studies. Here we sought to establish how chronic psychosocial stress influences fentanyl consumption in male and female C57BL/6 mice. We used chronic social defeat stress (CSDS), or the modified vicarious chronic witness defeat stress (CWDS), and used social interaction to stratify mice as stress-susceptible or resilient. We then subjected mice to a 15 days fentanyl drinking paradigm in the home cage that consisted of alternating forced and choice periods with increasing fentanyl concentrations. Male mice susceptible to either CWDS or CSDS consumed more fentanyl relative to unstressed mice. CWDS-susceptible female mice did not differ from unstressed mice during the forced periods, but showed increased preference for fentanyl over time. We also found decreased expression of nucleus accumbens Rho GTPases in male, but not female mice following stress and fentanyl drinking. We also compare fentanyl drinking behavior in mice that had free access to plain water throughout. Our results indicate that stress-sensitized fentanyl consumption is dependent on both sex and behavioral outcomes to stress.

show abstract

“…Both chronic stress and opioid exposure cause structural changes in the nucleus accumbens (NAc) that are thought to drive stress-susceptibility or increased drug intake (Matsubara et al, 1999;Robinson et al, 2002;Spiga et al, 2005;Diana et al, 2006;Christoffel et al, 2011bChristoffel et al, , 2011aPal and Das, 2013;Golden et al, 2013;Guegan et al, 2016;Kobrin et al, 2016;Graziane et al, 2016;Francis et al, 2017;Cahill et al, 2018;Geoffroy et al, 2019;Fox et al, 2020aFox et al, , 2020b. We thus examined the consequences of our combined stress and fentanyl paradigm on genes associated with dendritic remodeling (Nakayama et al, 2000;Negishi and Katoh, 2005;Newey et al, 2005;Chen and Firestein, 2007).…”

Section: Chronic Stress and Fentanyl Exposure Downregulate Dendritic Complexity Molecules In The Nucleus Accumbensmentioning

confidence: 99%

Chronic Physical and Vicarious Psychosocial Stress Alter Fentanyl Consumption and Nucleus Accumbens Rho GTPases in Male and Female C57BL/6 Mice

Franco

Wulff

Lobo

et al. 2021

Preprint

View full text Add to dashboard Cite

Chronic stress can increase the risk of developing a substance use disorder in vulnerable individuals. Numerous models have been developed to probe the underlying neurobiological mechanisms, however most prior work has been restricted to male rodents, conducted only in rats, or introduces physical injury that can complicate opioid studies. Here we sought to establish how chronic psychosocial stress influences fentanyl consumption in male and female C57BL/6 mice. We used chronic social defeat stress (CSDS), or the modified vicarious chronic witness defeat stress (CWDS), and used social interaction to stratify mice as stress-susceptible or resilient. We then subjected mice to a 15 day fentanyl drinking paradigm in the home cage that consisted of alternating forced and choice periods with increasing fentanyl concentrations. Male mice susceptible to either CWDS or CSDS consumed more fentanyl relative to unstressed mice, and exhibited increased preference for fentanyl. CWDS-susceptible female mice did not differ from unstressed mice during the forced periods, but showed increased preference for fentanyl. We also found decreased expression of nucleus accumbens Rho GTPases in male, but not female mice following stress and fentanyl drinking. We also compare fentanyl drinking behavior in mice that had free access to plain water throughout. Our results indicate that stress-sensitized fentanyl consumption is dependent on both sex and behavioral outcomes to stress.

show abstract

Withdrawal from repeated morphine administration augments expression of the RhoA network in the nucleus accumbens to control synaptic structure

Abstract: Open Science: This manuscript was awarded with the Open Materials Badge. For more information see: https://cos.io/our-services/open-science-badges/.

Cited by 18 publications

References 43 publications

RiboTag-Seq Reveals a Compensatory cAMP Responsive Gene Network in Striatal Microglia Induced by Morphine Withdrawal

RiboTag-Seq Reveals a Compensatory cAMP Responsive Gene Network in Striatal Microglia Induced by Morphine Withdrawal

Chronic Physical and Vicarious Psychosocial Stress Alter Fentanyl Consumption and Nucleus Accumbens Rho GTPases in Male and Female C57BL/6 Mice

Chronic Physical and Vicarious Psychosocial Stress Alter Fentanyl Consumption and Nucleus Accumbens Rho GTPases in Male and Female C57BL/6 Mice

Contact Info

Product

Resources

About