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

The c-fos gene is expressed in the central nervous system in response to va rious neuronal stimuli. Using in situ hybridization, we examined the effect s of chronic morphine treatment and withdrawal on c-fos mRNA in the rat bra in, acid particularly within identified striatal neurons. Morphine dependen ce was induced by subcutaneous implantation of two pellets of morphine for 6 days and withdrawal was precipitated by administration of naltrexone. Pla cebo animals and morphine-dependent rats showed a very weak c-fos mRNA expr ession in all the structures studied. Our study emphasized the spatial vari ations in c-fos mRNA expression, and also revealed a peak expression of c-f os mRNA at 1 h after naltrexone-precipitated withdrawal in the projection a reas of dopaminergic neurons, noradrenergic neurons and in several regions expressing opiate receptors. Interestingly, morphine withdrawal induces c-f os mRNA expression in the two efferent populations of the striatum (i.e. st riatonigral and striatopallidal neurons) both in the caudate putamen and nu cleus accumbens. Moreover, the proportions of activated neurons during morp hine withdrawal are different in the caudate putamen (mostly in striatopall idal neurons) and in the shell and core parts of the nucleus accumbens (mos tly in striatonigral neurons). The activation of striatopallidal neurons su ggests a predominant dopaminergic regulation on c-fos gene expression in th e striatum during withdrawal. On the contrary, c-fos induction in striatoni gral neurons during withdrawal seems to involve a more complex regulation l ike opioid-dopamine interactions via the mu opioid receptor and the D1 dopa mine receptor coexpressed on this neuronal population or the implication of other neurotransmitter systems.