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Lesion Study of the Distribution of Serotonin 5-HT4 Receptors in Rat Basal Ganglia and Hippocampus

Authors

  • Valérie Compan,

    1. CNRS UPR 9013,‘Laboratoire de Neurobiologie Cellulaire et Fonctionnelle’BP, 71–31 Chemin Joseph Aiguier, 13402 Marseille Cedex 09, France
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  • Annie Daszuta,

    1. CNRS UPR 9013,‘Laboratoire de Neurobiologie Cellulaire et Fonctionnelle’BP, 71–31 Chemin Joseph Aiguier, 13402 Marseille Cedex 09, France
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  • Pascal Salin,

    1. CNRS UPR 9023,‘Mécanismes Moléculaires des Communications Cellulaires', CCIPE, Rue de la Cardonille, 34094 Montpelier Cedex 5, France
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  • Michèle Sebben,

    1. CNRS UPR 9023,‘Mécanismes Moléculaires des Communications Cellulaires', CCIPE, Rue de la Cardonille, 34094 Montpelier Cedex 5, France
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  • Joël Bockaert,

    Corresponding author
    1. CNRS UPR 9023,‘Mécanismes Moléculaires des Communications Cellulaires', CCIPE, Rue de la Cardonille, 34094 Montpelier Cedex 5, France
      Joel Bockaert, as above.
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  • Aline Dumuis

    1. CNRS UPR 9023,‘Mécanismes Moléculaires des Communications Cellulaires', CCIPE, Rue de la Cardonille, 34094 Montpelier Cedex 5, France
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Joel Bockaert, as above.

Abstract

The regional distribution of 5-hydroxytryptamine (5-HT4) receptors labelled with [3H]GR113808 was examined in rat basal ganglia and hippocampus after specific lesions. Lesion of serotonin neurons induced by injections of 5,7-dihydroxytryptamine into the dorsal and medial raphe nuclei resulted in increased 5-HT4 receptor binding in most regions examined, compared with controls. More precisely, there was a 78% increase in the rostral but no change in the caudal part of caudate-putamen, and 83% and 54% increases in the shell and core of the nucleus accumbens respectively. In the substantia nigra, the increase in 5-HT4 binding was larger (72%) than that in the globus pallidus (32%). In the hippocampus, 63%, 30% and 28% increases were measured in CA2, CA1 and CA3 respectively. Following lesion of dopamine neurons by intranigral injection of 6-hydroxydopamine, increased 5-HT4 receptor binding was observed in the caudal (59%), but not the rostral part of caudate-putamen, as well as in the globus pallidus (93%). Since no decreases in 5-HT4 receptor density were detected after the dopamine lesion, it was concluded that these receptors are not expressed in dopamine neurons. Kainic acid lesions of the caudate-putamen were associated with dramatic local decreases in 5-HT4 receptor binding on the injected side (-89%), which suggested that striatal neurons express 5-HT4 receptors. Corresponding decreases of 72 and 20% in receptor density were detected in globus pallidus and substantia nigra, consistent with a presumed localization of 5-HT4 receptors on striatal GABA neurons projecting to these regions. In the substantia nigra, the decrease in [3H]GR113808 binding was localized to the pars lateralis, indicating that striatal neurons belonging to the cortico-striato-nigrotectal pathway, and containing GABA and dynorphin, express 5-HT4 receptors.

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