Resumo

The nucleus accumbens (Acb) is a key structure of the reward system and is involved in different aspects of adaptative and emotional behaviors. Traditionally, the Acb is thought to be formed by two major territories, denominated core (AcbC) and shell (AcbSh). In both of them the bulk of neurons are medium spiny projection neurons (MSNs) that receive converging dopaminergic and glutamatergic inputs and are modulated by different types of GABAergic and cholinergic interneurons. Nowadays, there is increasing evidence from hodological and immunohistochemical studies that the AcbSh, and in particular its caudal part, is a highly heterogeneous structure that consists of several distinct subdivisions, transition areas, and microcircuits. To further clarify the internal organization of the Acb and the structural basis of dopamine-glutamate-GABA interactions, we investigated first by immunohistochemical methods the distribution of markers of the dopaminergic system, such as tyrosine hydroxylase (TH) and DARPP-32, of specific markers for accumbal interneurons, such as calretinin (Calr), parvalbumin (Parv) and acetylcholine, as well as the most common AMPA (GluR1, GluR2, GluR2/3, GluR4) and NMDA (NMDAR1) type glutamate (Glu) receptor subunits. Then we investigated by double-immunofluorescence techniques the co-localization of these Glu receptor subunits with the neuronal phosphoprotein DARPP-32, a reliable marker for MSNs, as well as with selected markers for interneurons. Adult male Wistar rats (n = 53) were perfused with 4% paraformaldehyde. Brain sections through the Acb were incubated with antibodies to the different markers used. Standard immunoperoxidase and immunofluorescence techniques were used for visualization. Among the AMPA type subunits GluR2/3 were the most widely distributed in the AcbSh and AcbC, whereas GluR1 and GluR4 showed a more restricted distribution. The main results of our co-localization studies were: (1.) all DARPP-32+ MSNs express GluR2/3 but not GluR1 and GluR4; (2.) GluR2/3 is colocalized with NMDAR1 but is not expressed in cholinergic and Parv+ interneurons; (3.) all Parv+ interneurons contain GluR1 and GluR4; (4.) microregions poor in TH and Calr coincide with areas with dense cell packing and strong GluR2/3 immunoreactivity that form in the caudal AcbSh a medial and lateral corridor system. These findings suggest that MSNs and interneurons of the Acb differ with regard to the combinations of AMPA type subunits expressed. Our results further characterize the caudal AcbSh as a highly heterogeneous structure and outline a complex system of GluR2/3 rich/TH-poor continuous corridors in the caudal AcbSh, in which dopaminergic neurotransmission might predominantly occur by volume transmission.