Get access

Mapping of c-fos gene expression in the brain during morphine dependence and precipitated withdrawal, and phenotypic identification of the striatal neurons involved

Authors

  • François Georges,

    1. Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5541, BP28, Laboratoire d'Histologie-Embryologie et de Neuropsychobiologie de Désadaptations, Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France
    Search for more papers by this author
  • Luis Stinus,

    1. Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5541, BP28, Laboratoire d'Histologie-Embryologie et de Neuropsychobiologie de Désadaptations, Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France
    Search for more papers by this author
  • Catherine Le Moine

    1. Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5541, BP28, Laboratoire d'Histologie-Embryologie et de Neuropsychobiologie de Désadaptations, Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France
    Search for more papers by this author

: Dr Catherine Le Moine, as above.
E-mail: catherine.lemoine@umr5541.u-bordeaux2.fr

Abstract

The c-fos gene is expressed in the central nervous system in response to various neuronal stimuli. Using in situ hybridization, we examined the effects of chronic morphine treatment and withdrawal on c-fos mRNA in the rat brain, and particularly within identified striatal neurons. Morphine dependence was induced by subcutaneous implantation of two pellets of morphine for 6 days and withdrawal was precipitated by administration of naltrexone. Placebo animals and morphine-dependent rats showed a very weak c-fos mRNA expression in all the structures studied. Our study emphasized the spatial variations in c-fos mRNA expression, and also revealed a peak expression of c-fos mRNA at 1 h after naltrexone-precipitated withdrawal in the projection areas of dopaminergic neurons, noradrenergic neurons and in several regions expressing opiate receptors. Interestingly, morphine withdrawal induces c-fos mRNA expression in the two efferent populations of the striatum (i.e. striatonigral and striatopallidal neurons) both in the caudate putamen and nucleus accumbens. Moreover, the proportions of activated neurons during morphine withdrawal are different in the caudate putamen (mostly in striatopallidal neurons) and in the shell and core parts of the nucleus accumbens (mostly in striatonigral neurons). The activation of striatopallidal neurons suggests a predominant dopaminergic regulation on c-fos gene expression in the striatum during withdrawal. On the contrary, c-fos induction in striatonigral neurons during withdrawal seems to involve a more complex regulation like opioid–dopamine interactions via the µ opioid receptor and the D1 dopamine receptor coexpressed on this neuronal population or the implication of other neurotransmitter systems.

Get access to the full text of this article

Ancillary