title: Cellular localization and distribution of dopamine D(4) receptors in the rat cerebral cortex and their relationship with the cortical dopaminergic and noradrenergic nerve terminal networks.
abstract: The role of the dopamine D(4) receptor in cognitive processes and its association with several neuropsychiatric disorders have been related to its preferential localization in the cerebral cortex. In the present work we have studied in detail the regional and cellular localization of the dopamine D(4) receptor immunoreactivity (IR) in the rat cerebral cortex and its relationship to the dopaminergic and noradrenergic nerve terminal networks, since both dopamine and noradrenaline have a high affinity for this receptor. High levels of D(4) IR were found in motor, somatosensory, visual, auditory, temporal association, cingulate, retrosplenial and granular insular cortices, whereas agranular insular, piriform, perirhinal and entorhinal cortices showed low levels. D(4) IR was present in both pyramidal and non-pyramidal like neurons, with the receptor being mainly concentrated to layers II/III. Layer I was observed to be exclusively enriched in D(4) IR branches of apical dendrites. Finally, mismatches were observed between D(4) IR and tyrosine hydroxylase and dopamine beta-hydroxylase IR nerve terminal plexuses, indicating that these receptors may be activated at least in part by dopamine and noradrenaline operating as volume transmission signals. The present findings support a major role of the dopamine D(4) receptor in mediating the transmission of cortical dopamine and noradrenaline nerve terminal plexuses.
authors.affiliation: Department of Cell Biology, Faculty of Sciences, University of Málaga, Campus de Teatinos s/n, 29071 Málaga, Spain. arivera@uma.es
authors.forename: A
authors.initials: A
authors.lastname: Rivera
authors.forename: A
authors.initials: A
authors.lastname: Peñafiel
authors.forename: M
authors.initials: M
authors.lastname: Megías
authors.forename: L F
authors.initials: LF
authors.lastname: Agnati
authors.forename: J F
authors.initials: JF
authors.lastname: López-Téllez
authors.forename: B
authors.initials: B
authors.lastname: Gago
authors.forename: A
authors.initials: A
authors.lastname: Gutiérrez
authors.forename: A
authors.initials: A
authors.lastname: de la Calle
authors.forename: K
authors.initials: K
authors.lastname: Fuxe
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism; D009411:Nerve Endings / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050638:Receptors, Dopamine D4 / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D000071246:Uncoupling Protein 2; D050638:Receptors, Dopamine D4; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D004298:Dopamine; D009638:Norepinephrine