Elsevier

Brain Research

Volume 688, Issues 1–2, 7 August 1995, Pages 95-104
Brain Research

Acute administration of typical and atypical antipsychotic drugs induces distinctive patterns of Fos expression in the rat forebrain

https://doi.org/10.1016/0006-8993(95)00544-ZGet rights and content

Abstract

Fos expression in the rat brain was investigated by immunohistochemistry after i.p. administration of single doses of a wide range of typical neuroleptic antipsychotic drugs (including the potent dopamine D2 antagonist haloperidol and the mixed monoamine antagonist chlorpromazine) and atypical antipsychotic drugs (including the weak dopamine D2 antagonists clozapine and thioridazine, the relatively pure D2 antagonist raclopride and the mixed D2 and serotonin S2 antagonist risperidone). For comparison to the effects of the antipsychotic drugs and also because the unique clinical therapeutic effects of clozapine have been attributed to S2 blockade, the S2 antagonist ritanserin was also studied. The single shared effect of all antipsychotic drugs tested was the induction of significantly increased Fos immunoreactivity in the nucleus accumbens (NAc). Fos-positive neurons in the NAc were mostly localized in patches throughout its rostrocaudal extent. Haloperidol, chlorpromazine, raclopride and risperidone all significantly increased Fos expression in the medial and lateral striatum. Fos-positive neurons in the striatum were distributed more lateral than medial and declined from rostral to caudal levels. Haloperidol, thioridazine and risperidone also markedly increased Fos expression in the lateral septum. Distinguishing it from the other neuroleptics, clozapine did not increase Fos expression in the lateral striatum, but induced a significant increase in Fos expression in the prefrontal cortex. Ritanserin did not induce Fos expression in any brain region examined, suggesting that S2 antagonism is not responsible for the effects of antipsychotic drugs observed here. Our results suggest that there are distinctive patterns of Fos expression in the forebrain induced by typical and atypical antipsychotic drugs. Notably, Fos expression in the NAc, as a shared property of all the antipsychotic drugs, may be related to the actions mediating the therapeutic effects of these drugs in the treatment of psychotic disorders. The density of Fos-positive neurons stimulated by antipsychotic drugs in the striatum appeared to be correlated with the relative severity of extrapyramidal side-effects produced by these drugs and may be related to the mechanisms mediating these effects.

References (52)

  • LandwehrmeyerB. et al.

    Dopamine D3 receptor mRNA and binding sites in human brain

    Mol. Brain Res.

    (1993)
  • LeslieR.A. et al.

    Serotonin2/1c receptor activation causes a localized expression of the immediate-early gene c-fos in rat brain: evidence for involvement of dorsal raphe nucleus projection fibres

    Neuroscience

    (1993)
  • MacGibbonG.A. et al.

    Clozapine and haloperidol produce a differential pattern of immediate early gene expression in rat caudate-putamen, nucleus accumbens, lateral septum and islands of Calleja

    Mol. Brain Res.

    (1994)
  • MatthysseS.

    Dopamine and the pharmacology of schizophrenia: the state of evidence

    J. Psychiatr. Res.

    (1974)
  • MorganJ.I. et al.

    Stimulus-transcription coupling in neurons: role of cellular immediate-early genes

    Trends Neurosci.

    (1989)
  • PazosA. et al.

    Quantitative autoradiographic mapping of serotonin receptors in the rat brain. II. Serotonin-2-receptors

    Brain Res.

    (1985)
  • RobertsonG.H. et al.

    L-Dopa activates c-fos in the striatum ipsilateral to a 6-hydroxydopamine lesion of the substantia nigra

    Eur. J. Pharmacol.

    (1989)
  • RobertsonG.S. et al.

    Neuroleptics increase c-fos expression in the forebrain: contrasting effects of haloperidol and clozapine

    Neuroscience

    (1992)
  • RobertsonH.A. et al.

    D1-dopamine receptor agonists selectively activate striatal c-fos independent of rotational behaviour

    Brain Res.

    (1989)
  • ShengM. et al.

    The regulation and function of c-fos and other immediate early genes in the nervous system

    Neuron

    (1990)
  • WanW. et al.

    Differential induction of c-fos immunoreactivity in hypothalamus and brain stem nuclei following central and peripheral administration of endotoxin

    Brain Res. Bull.

    (1993)
  • BoysonS.J. et al.

    Quantitative autoradiographic localization of the D1 and D2 subtypes of dopamine receptors in rat brain

    J. Neurosci.

    (1986)
  • BrownI.H.

    Atropine, scopolamine, and related antimuscarinic drugs

  • ClausA. et al.

    Risperidone versus haloperidol in the treatment of chronic schizophrenic inpatients: a multicenter double-blind comparative study

    Acta Psychiatr. Scand.

    (1992)
  • CreeseI. et al.

    Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs

    Science

    (1976)
  • DursunS.M. et al.

    Comparison of ritanserin, haloperidol, pimozide and clonidine on spontaneous and DOI head-shake

    Br. J. Pharmacol.

    (1992)
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