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

Lubbers BR, Matos MR, Horn A, Visser E, Van Der Loo RC, Gouwenberg Y, Meerhoff GF, Frischknecht R, Seidenbecher CI, Smit AB, Spijker S, Van Den Oever MC (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Neuropsychopharmacology Nature Publishing Group: Open Access Hybrid Model Option A

Book Volume: 41

Pages Range: 1907-1916

Journal Issue: 7

DOI: 10.1038/npp.2015.361

Abstract

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 contextual-fear 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. Post-conditioning 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.

Involved external institutions

Vrije Universiteit Amsterdam (VU) / University Amsterdam NL Netherlands (NL) Max-Planck-Institut für Neurobiologie / Max Planck Institute of Neurobiology DE Germany (DE)

How to cite

APA:

Lubbers, B.R., Matos, M.R., Horn, A., Visser, E., Van Der Loo, R.C., Gouwenberg, Y.,... Van Den Oever, M.C. (2016). The Extracellular Matrix Protein Brevican Limits Time-Dependent Enhancement of Cocaine Conditioned Place Preference. Neuropsychopharmacology, 41(7), 1907-1916. https://dx.doi.org/10.1038/npp.2015.361

MLA:

Lubbers, Bart R., et al. "The Extracellular Matrix Protein Brevican Limits Time-Dependent Enhancement of Cocaine Conditioned Place Preference." Neuropsychopharmacology 41.7 (2016): 1907-1916.

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