Environmental enrichment decreases the rewarding but not the activating effects of heroin

Abstract

Rationale

Environmental conditions during adolescence, a critical period of brain maturation, can have important consequences on subsequent vulnerability to drugs of abuse. We have recently found that the behavioral effects of cocaine as well as its ability to increase expression of zif-268 are reduced in mice reared in enriched environments (EE).

Objectives

The present experiments examined whether environmental enrichment has protective influences on the effects of heroin, a drug of addiction whose mechanism of action differs from that of cocaine.

Materials and methods

Mice were housed either in standard environments (SE) or in EE from weaning to adulthood before any drug exposure. EE were constituted by big housing cages and contained constantly a running wheel and a small house and four to five toys that were changed once a week with new toys of different shapes and colors. We assessed the influence of EE on the ability of heroin to (1) induce conditioned place preferences, (2) induce behavioral sensitization, (3) increase dopamine levels in the nucleus accumbens (NAc), and (4) increase expression of the immediate early gene zif-268 in the striatum.

Results

Conditioned place preference but not behavioral sensitization was reduced in EE mice compared to SE mice. Heroin induced similar increases in dopamine levels and in the expression of zif-268 in the NAc of EE and SE mice.

Conclusions

The rewarding effects of heroin are blunted by EE and appear to be, at least in part, independent from activation of the mesolimbic system.

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Acknowledgments

The authors acknowledge the support given by Fondation pour la Recherche Médicale (FRM, 2003), Mission Interministérielle de la Lutte contre les Drogues et la Toxicomanie (MILDT-INSERM, 2006–2007), and Région Poitou Charentes (2003). R. El Rawas is a recipient of a CNRS Ph.D. fellowship (BDI-PED, 2005–2008).

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Correspondence to Marcello Solinas.

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El Rawas, R., Thiriet, N., Lardeux, V. et al. Environmental enrichment decreases the rewarding but not the activating effects of heroin. Psychopharmacology 203, 561–570 (2009). https://doi.org/10.1007/s00213-008-1402-6

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Keywords

  • Drug addiction
  • Opiates
  • Enriched environments
  • Conditioned place preference
  • Behavioral sensitization
  • Dopamine
  • Nucleus accumbens
  • In vivo microdialysis
  • In situ hybridization
  • Zif-268