Synaptic plasticity mediating cocaine relapse requires matrix metalloproteinases

Smith, Alexander C.W.; Kupchik, Yonatan M.; Scofield, Michael D.; Gipson, Cassandra D.; Wiggins, Armina; Thomas, Charles A.; Kalivas, Peter W.

doi:10.1038/nn.3846

Cited by 122 publications

(181 citation statements)

References 27 publications

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“…Animal models confirm changes in MMP expression following exposure to drugs of abuse and their involvement in drug-associative memories and relapse to drug seeking (Brown et al, 2007;Smith et al, 2014;Van den Oever et al, 2010). Much less is known about the contribution of structural ECM components to addictive behavior.…”

Section: Introductionmentioning

confidence: 90%

“…Remodelling of the ECM at perisynaptic sites is thought to contribute to mechanisms of synaptic plasticity and addictive behavior (Smith et al, 2014;Van den Oever et al, 2010). Therefore, we determined whether infusion of AAV-Bcan in the mPFC resulted in increased brevican levels in total protein homogenates and synaptosome-enriched fractions of the mPFC by immunoblotting (Figure 3f-i) 4 weeks post surgery.…”

Section: Overexpression Of Brevican In the Mpfcmentioning

confidence: 99%

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The Extracellular Matrix Protein Brevican Limits Time-Dependent Enhancement of Cocaine Conditioned Place Preference

Lubbers

Matos

Horn

et al. 2015

Neuropsychopharmacol

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Cocaine-associated environmental cues sustain relapse vulnerability by reactivating long-lasting memories of cocaine reward. During periods of abstinence, responding to cocaine cues can time-dependently intensify a phenomenon referred to as 'incubation of cocaine craving'. Here, we investigated the role of the extracellular matrix protein brevican in recent (1 day after training) and remote (3 weeks after training) expression of cocaine conditioned place preference (CPP). Wild-type and Brevican heterozygous knock-out mice, which express brevican at~50% of wild-type levels, received three cocaine-context pairings using a relatively low dose of cocaine (5 mg/kg). In a drug-free CPP test, heterozygous mice showed enhanced preference for the cocaine-associated context at the remote time point compared with the recent time point. This progressive increase was not observed in wild-type mice and it did not generalize to contextualfear memory. Virally mediated overexpression of brevican levels in the hippocampus, but not medial prefrontal cortex, of heterozygous mice prevented the progressive increase in cocaine CPP, but only when overexpression was induced before conditioning. Postconditioning overexpression of brevican did not affect remote cocaine CPP, suggesting that brevican limited the increase in remote CPP by altering neuro-adaptive mechanisms during cocaine conditioning. We provide causal evidence that hippocampal brevican levels control time-dependent enhancement of cocaine CPP during abstinence, pointing to a novel substrate that regulates incubation of responding to cocaine-associated cues.

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Section: Introductionmentioning

confidence: 90%

Section: Overexpression Of Brevican In the Mpfcmentioning

confidence: 99%

The Extracellular Matrix Protein Brevican Limits Time-Dependent Enhancement of Cocaine Conditioned Place Preference

Lubbers

Matos

Horn

et al. 2015

Neuropsychopharmacol

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“…Blood or brain tissue MMP-9 levels were found to be increased in such human disorders as cocaine addiction, epilepsy, and depression. [23][24][25][26] A link to human neuropsychiatric diseases has also been suggested. For example, MMP-9 gene polymorphisms have been implicated in alcohol addiction and bipolar disorder.…”

Section: Mmp-9 In Human Neuropsychiatric Disordersmentioning

confidence: 99%

Matrix Metalloproteinase-9 as a Novel Player in Synaptic Plasticity and Schizophrenia: Table 1.

Lepeta¹,

Kaczmarek²

2015

SCHBUL

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Recent findings implicate alterations in glutamate signaling, leading to aberrant synaptic plasticity, in schizophrenia. Matrix metalloproteinase-9 (MMP-9) has been shown to regulate glutamate receptors, be regulated by glutamate at excitatory synapses, and modulate physiological and morphological synaptic plasticity. By means of functional gene polymorphism, gene responsiveness to antipsychotics and blood plasma levels MMP-9 has recently been implicated in schizophrenia. This commentary critically reviews these findings based on the hypothesis that MMP-9 contributes to pathological synaptic plasticity in schizophrenia.Key words: synaptic plasticity/glutamate/extracellular matrix Matrix Metalloproteinase-9 in Animal Studies Matrix Metalloproteinase-9 Expression and Activity in the BrainMatrix metalloproteinase-9 (MMP-9) belongs to a family of zinc-dependent proteases, mostly secreted as inactive pro-enzymes, activated outside the cell upon proteolytic cleavage. MMPs degrade extracellular matrix constituents, other proteases, growth factors, and extracellular domains of transmembrane proteins, such as cell adhesion molecules and receptors. As a result, MMPs participate in remodeling the pericellular microenvironment and cell-signaling via either the release or processing (to reveal their binding domains) of cell-surface receptor ligands.

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“…Wisteria Floribunda agglutinin (WFA) or Vicia Villosa agglutinin (VVA) that are lectins which bind to the sugar chains of CSPGs Notably, although PNNs are highly stable structures resistant to classic enzymatic degradation systems, there are specific enzymes which are able to modify their structure and function Smith et al, 2014). Matrix metalloproteases (MMPs) are enzymes that degrade the ECMs as well as other molecules expressed on the cell surface.…”

Section: Pnn Structure and Regulation Mechanismsmentioning

confidence: 99%

“…MMP levels were also assessed in the striatum of rats under withdrawal from cocaine self-administration (SA) and cue-induced reinstatement of drug-seeking behavior. While MMP-2 was upregulated after the withdrawal period, an increase in MMP-9 levels were found during cue-induced reinstatement of different types of drugs (Smith et al, 2014). Studies that have manipulated pharmacologically MMP activity using the infusion of a broadspectrum MMP inhibitor show that blocking MMP activity before conditioning sessions suppresses cocaine-induced CPP, and abolished cocaine-primed reinstatement when the injection was made just before the reinstatement session .…”

Section: The Involvement Of Pnns In Drug Addictionmentioning

confidence: 99%

Involvement of the cerebellum in cocaine-induced memory

Gas¹

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PREFACEBecause of its role in drug-seeking, consumption and addictive behavior, there is a growing interest in identifying the neural circuits and molecular mechanisms underlying the formation, maintenance and retrieval of drug-induced memories. However, very few studies have focused on brain areas beyond the corticostriatal-limbic circuitry. Despite the growing evidence confirming the involvement of the cerebellum in drug-induced alterations, this structure has been traditionally disregarded in the addiction field Miquel et al, 2016).The general aim of the present research is to address wether the cerebellum is part of the neuronal systems that sustains the plasticity mechanisms underlying drug-induced conditioned memories. We have focused our research in an attempt to clarify if the cerebellum is involved in the acquisition and storage of drug memories. Although previous scattered reports described the involvement of the cerebellum in drug-related memories, this is the first attempt to address a detailed functional analysis about the issue.The present doctoral thesis contains three different chapters. The first two include two investigations that have been already published (Carbo-gas et al., 2014ab), and the third is one currently under revision. In the first chapter, Involving the cerebellum in cocaineinduced memory: pattern of cFos expression in mice trained to acquire conditioned preference for cocaine, we explored the pattern of neuronal activation as revealed by cFos immunoreactivity of mice trained to develop conditioned preference for an olfactory stimulus paired with cocaine. In the second one, entitled Cerebellar hallmarks of conditioned preference for cocaine, we used the same behavioral task of the first study in order to further extend the description of cFos expression patterns in cerebellar circuitry, including now the major inputs and one of the output nuclei of the cerebellum. 9In the last chapter, Cerebellar perineuronal nets in cocaine-induced Pavlovian memory:site does matter, we accomplished a broad analysis of perineuronal nets (PNNs) expression of cerebellar vermis. First, we analysed an outbred mouse strain trained to acquire preference for olfactory stimuli associated with cocaine. Second, α6Cre-Cacna1a mice were used to test if a reduction in the glutamate release of parallel fibres to Purkinje dendrites would alter the acquisition of cocainepreference conditioning and the expression of PNNs in the cerebellum.After the presentation of the chapters, there is a section where summarised findings, strengths and pitfalls as well as future directions are provided. References can be also found at the end of the present document.Finally, we conclude this thesis with an appendix. This document is formed by research not finished yet, but that may be of great relevance to understand the role of the cerebellum in addictive disorders. In that appendix, we explored the effect of a focal lesion in the dorsal cerebellar cortex (Lobule VIII) on the acquisition of food selfadministration. This researc...

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Synaptic plasticity mediating cocaine relapse requires matrix metalloproteinases

Cited by 122 publications

References 27 publications

The Extracellular Matrix Protein Brevican Limits Time-Dependent Enhancement of Cocaine Conditioned Place Preference

The Extracellular Matrix Protein Brevican Limits Time-Dependent Enhancement of Cocaine Conditioned Place Preference

Matrix Metalloproteinase-9 as a Novel Player in Synaptic Plasticity and Schizophrenia: Table 1.

Involvement of the cerebellum in cocaine-induced memory

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