Minocycline prevents chronic restraint stress-induced vulnerability to developing cocaine self-administration and associated glutamatergic mechanisms: a potential role of microglia

Avalos, María Paula; Guzmán, Andrea S.; Rigoni, Daiana; Gorostiza, Ezequiel Axel; Sanchez, Marianela A; Mongi‐Bragato, Bethania; García‐Keller, Constanza; Perassi, Eduardo Marcelo; Virgolini, Miriam Beatríz; Ramos, Javier María Peralta; Iribarren, Pablo; Calfa, Gastón; Bollati, Flavia; Cancela, Liliana Marina

doi:10.1016/j.bbi.2022.01.014

Cited by 9 publications

(12 citation statements)

References 122 publications

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“…Likewise, here we found similar results to ARS when we studied basal extracellular glutamate concentrations in the NAcore. Even more, we confirmed that GLT-1 is reduced by 30% in the NAcore long after the CRS regime, a result also consistent with our most recent published data (Avalos et al, 2022). Interestingly, an equivalent downregulated glutamate transport was observed in acutely restrained animals without experiencing a cocaine challenge (Garcia-Keller et al, 2016).…”

Section: Discussionsupporting

confidence: 92%

“…These alterations of glutamatergic mechanisms were related to a decreased expression of GLT-1 in the NAcore. All these results proved to be highly consistent and also matched previous data from our laboratory concerning crosssensitization between ARS or CRS and cocaine (Avalos et al, 2022;Garcia-Keller et al, 2013, 2016. For instance, resembling dopamine assessment obtained in our laboratory when comparing cocaine-evoked dopamine release after ARS or CRS, a comparable response to that observed after ARS protocol concerning the glutamate efflux following a cocaine i.p.…”

Section: Discussionsupporting

confidence: 91%

“…Glutamate transmission has also been considered a critical hub for the effects of stress on behavior. An altered glutamate homeostasis in the NAcore was related to stress-induced addictive behaviors associated with cocaine administration (Esparza et al, 2012;Garcia-Keller et al, 2013, 2016Rigoni et al, 2021;Avalos et al, 2022). These alterations recapitulate, in part, the glutamatergic mechanisms triggered by repeated exposure to psychostimulants (Pierce et al, 1996;Knackstedt et al, 2010;Wang et al, 2017;Prieto et al, 2020).…”

Section: Introductionmentioning

confidence: 92%

“…Epidemiological evidence points out a link between stressful events and drug abuse in humans (Clark et al, 2001;Boden et al, 2012). In animal models, the fact that different types of stressors and stress protocols are able to activate discrete neurobiological mechanisms to promote addictive behaviors (Pacchioni et al, 2007;Boyson et al, 2011Boyson et al, , 2014Esparza et al, 2012;Leão et al, 2012;Garcia-Keller et al, 2013, 2016Lo Iacono et al, 2018;Bertagna et al, 2021;Rigoni et al, 2021;Avalos et al, 2022) and trigger relapse to drugseeking behavior even after long periods of abstinence (Gysling, 2012;De Giovanni et al, 2016;Mantsch et al, 2016;Guzman et al, 2021) suggests that stress and addictive drugs impact on common neurobiological mechanisms.…”

Section: Introductionmentioning

confidence: 99%

“…All these persistent alterations thought to underlie addictive behaviors have been related to enduring adaptations in medium spiny neurons (MSNs) (Kalivas, 2009). Indeed, structural remodeling of dendritic spines has been linked to behavioral adaptations induced by motivationally relevant stimuli, such as drug administration and exposure to stress (Kalivas, 2009;Golden and Russo, 2012;Garcia-Keller et al, 2016;Fox et al, 2020;Rigoni et al, 2021;Avalos et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

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Impairment of glutamate homeostasis in the nucleus accumbens core underpins cross-sensitization to cocaine following chronic restraint stress

et al. 2022

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Though the facilitating influence of stress on drug abuse is well documented, the mechanisms underlying this interaction have yet to be fully elucidated. The present study explores the neurobiological mechanisms underpinning the sensitized response to the psychomotor-stimulating effects of cocaine following chronic restraint stress (CRS), emphasizing the differential contribution of both subcompartments of the nucleus accumbens (NA), the core (NAcore) and shell (NAshell), to this phenomenon. Adult male Wistar rats were restrained for 2 h/day for 7 days and, 2 weeks after the last stress exposure (day 21), all animals were randomly assigned to behavioral, biochemical or neurochemical tests. Our results demonstrated that the enduring CRS-induced increase in psychostimulant response to cocaine was paralleled by an increase of extracellular dopamine levels in the NAcore, but not the NAshell, greater than that observed in the non-stress group. Furthermore, we found that CRS induced an impairment of glutamate homeostasis in the NAcore, but not the NAshell. Its hallmarks were increased basal extracellular glutamate concentrations driven by a CRS-induced downregulation of GLT-1, blunted glutamate levels in response to cocaine and postsynaptic structural remodeling in pre-stressed animals. In addition, ceftriaxone, a known GLT-1 enhancer, prevented the CRS-induced GLT-1 downregulation, increased basal extracellular glutamate concentrations and changes in structural plasticity in the NAcore as well as behavioral cross-sensitization to cocaine, emphasizing the biological importance of GLT-1 in the comorbidity between chronic stress exposure and drug abuse. A future perspective concerning the paramount relevance of the stress-induced disruption of glutamate homeostasis as a vulnerability factor to the development of stress and substance use disorders during early life or adulthood of descendants is provided.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Impairment of glutamate homeostasis in the nucleus accumbens core underpins cross-sensitization to cocaine following chronic restraint stress

et al. 2022

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The HMGB1–RAGE axis in nucleus accumbens facilitates cocaine‐induced conditioned place preference via modulating microglial activation

Ye,

Gao,

Liu

et al. 2024

Brain and Behavior

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IntroductionRepeated exposure to cocaine induces microglial activation. Cocaine exposure also induces a release of high mobility group box‐1 (HMGB1) from neurons into the extracellular space in the nucleus accumbens (NAc). HMGB1 is an important late inflammatory mediator of microglial activation. However, whether the secretion of HMGB1 acts on microglia or contributes to cocaine addiction is largely unknown.MethodsRats were trained by intraperitoneal cocaine administration and cocaine‐induced conditioned place preference (CPP). Expression of HMGB1 was regulated by viral vectors. Activation of microglia was inhibited by minocycline. Interaction of HMGB1 and the receptor for advanced glycation end products (RAGE) was disrupted by peptide.ResultsCocaine injection facilitated HMGB1 signaling, together with the delayed activation of microglia concurrently in the NAc. Furthermore, the inhibition of HMGB1 or microglia activation attenuated cocaine‐induced CPP. Box A, a specific antagonist to interrupt the interaction of HMGB1 and RAGE, abolished the expression of cocaine reward memory. Meanwhile, the inhibition of HMGB1–RAGE interaction suppressed cocaine‐induced microglial activation, as well as the consolidation of cocaine‐induced memory.ConclusionAll above results suggest that the neural HMGB1 induces activation of microglia through RAGE, which contributes to the consolidation of cocaine reward memory. These findings offer HMGB1–RAGE axis as a new target for the treatment of drug addiction.

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Substance Use and Addiction

Newton,

De Biase

2024

Advances in Neurobiology

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Minocycline prevents chronic restraint stress-induced vulnerability to developing cocaine self-administration and associated glutamatergic mechanisms: a potential role of microglia

Cited by 9 publications

References 122 publications

Impairment of glutamate homeostasis in the nucleus accumbens core underpins cross-sensitization to cocaine following chronic restraint stress

Impairment of glutamate homeostasis in the nucleus accumbens core underpins cross-sensitization to cocaine following chronic restraint stress

The HMGB1–RAGE axis in nucleus accumbens facilitates cocaine‐induced conditioned place preference via modulating microglial activation

Substance Use and Addiction

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