Inhibition of the mammalian target of rapamycin pathway by rapamycin blocks cocaine-induced locomotor sensitization

Wu, Jinfang; McCallum, Sarah E.; Glick, Stanley D.; Huang, Yunfei

doi:10.1016/j.neuroscience.2010.10.041

Cited by 47 publications

(57 citation statements)

References 29 publications

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“…Bailey et al (2012) and Cui et al (2010) found that rapamycin attenuated the expression of the cocaine CPP and formation of morphine CPP. Also, Bailey et al (2012) and Wu et al (2011) found that inhibition of mTOR by rapamycin blocked the induction as well as the expression of cocaine-induced locomotor sensitization in rats. Wang et al (2009) indicated that the mTOR signaling pathway in the NAc core mediated cue-induced reinstatement of cocaine seeking in the rat self-administration model, and inhibition of its activity prevented drug seeking.…”

Section: Discussionmentioning

confidence: 97%

“…The mTOR signaling pathway has been implicated in regulating stimulant-induced sensitization and drug abuse disorder in rodents, as well as drug craving in abstinent heroin addicts (Shi et al, 2009;Wu et al, 2011;Bailey et al, 2012;Yu et al, 2013). Bailey et al (2012) and Cui et al (2010) found that rapamycin attenuated the expression of the cocaine CPP and formation of morphine CPP.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies have demonstrated that the mTOR signaling pathway is involved in the neuroadaptations that occur with longterm drug exposure. Pharmacologic inhibition of the mTOR pathway attenuates the induction or expression of drug CPP and behavioural sensitization (Cui et al, 2010;Bailey et al, 2012;Wu et al, 2011), and reduces cue-induced cocaine seeking behaviour (Wang et al, 2010). Therefore, in this study, using a typical protocol for drug reward memory, CPP, we examined the effect of rapamycin on reconsolidation of drug reward memory.…”

Section: Introductionmentioning

confidence: 99%

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Rapamycin prevents drug seeking via disrupting reconsolidation of reward memory in rats

Lin

Liu

Wen

et al. 2013

Int. J. Neuropsychopharm.

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The maladaptive drug memory developed between the drug-rewarding effect and environmental cues contributes to difficulty in preventing drug relapse. Established reward memories can be disrupted by pharmacologic interventions following their reactivation. Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) kinase, has been proved to be involved in various memory consolidation. However, it is less well characterized in drug memory reconsolidation. Using a conditioned place preference (CPP) procedure, we examined the effects of systemically administered rapamycin on reconsolidation of drug memory in rats. We found that systemically administered rapamycin (0.1 or 10 mg/kg, i.p.) after re-exposure to drug-paired environment, dose dependently decreased the expression of CPP 1 d later, and the effect lasted for up to 14 d and could not be reversed by a priming injection of morphine. The effect of rapamycin on morphine-associated memory was specific to drug-paired context, and rapamycin had no effect on subsequent CPP expression when rats were exposed to saline-paired context or homecage. These results indicated that systemic administration of rapamycin after memory reactivation can persistently inhibit the drug seeking behaviour via disruption of morphine memory reconsolidation in rats. Additionally, the effect of rapamycin on memory reconsolidation was reproduced in cocaine CPP and alcohol CPP. Furthermore, rapamycin did not induce conditioned place aversion and had no effect on locomotor activity and anxiety behaviour. These findings suggest that rapamycin could erase the acquired drug CPP in rats, and that mTOR activity plays an important role in drug reconsolidation and is required for drug relapse.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rapamycin prevents drug seeking via disrupting reconsolidation of reward memory in rats

Lin

Liu

Wen

et al. 2013

Int. J. Neuropsychopharm.

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“…Li treatment inhibits (phosphorylates) GSK3β activities in the NAc and blocks locomotor sensitization induced by MA [23]. Studies indicate that GSK3β can inhibit the phosphorylation of mTOR, which is also implicated in locomotor sensitization [37]. Therefore, we hypothesized that Akt/GSK3β/mTOR pathway may be implicated in MA exposure.…”

Section: Ly294002 Reduces the Protective Effects Of LImentioning

confidence: 97%

Lithium protects against methamphetamine-induced neurotoxicity in PC12 cells via Akt/GSK3β/mTOR pathway

Zhu

Zhang

et al. 2015

Biochemical and Biophysical Research Communications

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“…Depletion of mTOR or regulatory-associated protein of mTOR complex 1 (RPTOR; a key component of mTORC1) from specific neuronal populations reduced <m>locomotor sensitization</m> (one of the symptoms of cocaine administration) in mice 59 , as did rapamycin administration in rats 60 . By contrast, inhibition of autophagy with small interfering RNAs (siRNAs) targeting Atg5 or Becn1 limited the capacity of cocaine to trigger RCD in mouse primary cortical neurons 58 .…”

Section: Autophagy As a Therapeutic Targetmentioning

confidence: 99%

Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles

Galluzzi

Pedro

Levine

et al. 2017

Nat Rev Drug Discov

720

589

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Autophagy is central to the maintenance of organismal homeostasis in both physiological and pathological situations. Accordingly, alterations in autophagy have been linked to clinically relevant conditions as diverse as cancer, neurodegeneration and cardiac disorders. Throughout the past decade, autophagy has attracted considerable attention as a target for the development of novel therapeutics. However, such efforts have not yet generated clinically viable interventions. In this Review, we discuss the therapeutic potential of autophagy modulators, analyse the obstacles that have limited their development and propose strategies that may unlock the full therapeutic potential of autophagy modulation in the clinic.

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Inhibition of the mammalian target of rapamycin pathway by rapamycin blocks cocaine-induced locomotor sensitization

Cited by 47 publications

References 29 publications

Rapamycin prevents drug seeking via disrupting reconsolidation of reward memory in rats

Rapamycin prevents drug seeking via disrupting reconsolidation of reward memory in rats

Lithium protects against methamphetamine-induced neurotoxicity in PC12 cells via Akt/GSK3β/mTOR pathway

Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles

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