Regional and cellular distribution of serotonin 5-hydroxytryptamine2a receptor mRNA in the nucleus accumbens, olfactory tubercle, and caudate putamen of the rat

Abstract

This paper describes the regional and cellular distribution of serotonin 5-hydroxytryptamine2a (5-HT2a) receptor mRNA in (sub)regions of the rat striatum by using in situ hybridization. Our results indicate that 5-HT2a mRNA is distributed heterogeneously in this brain region. Regional densitometry of autoradiograms from striatal sections hybridized with isotope-labeled cRNA probes showed that mRNA levels were highest in the olfactory tubercle, lower in the nucleus accumbens, and lowest in the caudate-putamen. In the nucleus accumbens, the average mRNA levels in the shell were higher than those in the core. These data suggest a particular relevance for the 5-HT2a receptor for olfactory tubercle- and shell-related functions. Therefore, in the nucleus accumbens and the olfactory tubercle, the cellular localization of 5-HT2a mRNA was investigated by determining the colocalization of 5-HT2a mRNA with enkephalin mRNA or dynorphin mRNA. 5-HT2a mRNA was found in enkephalinergic as well as dynorphinergic neurons. Thus, there does not seem to be a differential distribution of this receptor in the output routes of the ventral striatum. In all of the subregions investigated (core, medial shell, and lateral shell of the nucleus accumbens and the olfactory tubercle), only subpopulations of the total enkephalinergic and dynorphinergic populations were found to contain 5-HT2a mRNA. For enkephalin, the percentage colocalization was higher in the lateral shell (61%) compared with the other subregions (38-45%). For dynorphin, the percentage colocalization was higher in the olfactory tubercle (68%) than in the other subregions (34-43%). The differences in (sub)regional mRNA levels and in colocalization with opioids suggest a considerable regional differentiation in the effects of 5-HT2a-mediated neurotransmission in the striatum.

Distribution of serotonin 5-HT2A receptors in afferents of the rat striatum

“…The myelinated fibers of corticostriatal axons were densely stained. Our observation that immunolabeling was restricted to relatively few scattered large 5-HT 2A -li neurons agrees with most in situ hybridization studies (Pompeiano et al, 1994;Wright et al, 1995;Laprade et al, 1996;Mijnster et al, 1997), which have found few cells expressing 5-HT 2A mRNA in the dorsal striatum. In the ventrolateral striatum and fundus striatum, however, 5-HT 2A mRNA-expressing medium spiny neurons are more frequently encountered (Mijnster et al, 1997).…”

“…Receptor binding and in situ hybridization histochemistry studies have revealed a widespread distribution of 5-HT 2A receptors in the brain (Pompeiano et al, 1994;Wright et al, 1995;Mengod et al, 1996;Ward and Dorsa, 1996;Mijnster et al, 1997;Roth et al, 1998). 5-HT 2A receptor binding is moderately high but 5-HT 2A mRNA levels are very low in the striatum, suggesting that 5-HT 2A receptors are localized primarily to striatal afferents.…”

Molecular mapping of striatal subdivisions in juvenile Macaca Mulata

“…A number of previous studies have employed this technique to investigate similar questions in different brain subregions, demonstrating the utility of this approach (Sandberg et al, 2000;Zhao et al, 2001). Previous studies of the striatum have used in situ hybridization and ribonuclease protection assays to examine a few transcriptional differences within the striatum on a gene by gene basis (Honrubia et al, 2000;Huntley et al, 1992;Kultas-Ilinsky et al, 1998;Mijnster et al, 1997;Rappaport et al, 1993;Richtand et al, 1995;Svenningsson et al, 1998;Wullner et al, 1997). The work presented here demonstrates the first large-scale molecular profiles for distinguishing subregions of the striatum in primates.…”

“…However, the molecular mechanisms underlying the diversity of function between the morphologically similar subregions of the striatum remains poorly understood. Several studies have described different gene and protein expression between the subregions with the greatest differences between the VS and CAU/PUT (Bouthenet et al, 1991;Glass et al, 1997;Joseph et al, 2003;Mijnster et al, 1997;Piggott et al, 1999;Richtand et al, 1995). Most likely, regional differences in the functional output of the basal ganglia result from a combination of differences in connectivity and differences in the abundances of specific transcripts and proteins.…”

The effects of benzofury (5-APB) on the dopamine transporter and 5-HT2-dependent vasoconstriction in the rat

“…The recording microelectrode was placed in the accumbens shell at the start of the equilibration period to monitor background dopamine levels, as under certain circumstances (such as poor slice health or increased temperature) large spontaneous release of dopamine can occur (Davidson et al, 2011). We recorded in the accumbens shell because 5-HT 2A receptors are most prevalent in this part of the striatum (Mijnster et al, 1997; and see Figure 1) and the shell is thought to show the greatest acute effect of stimulants (Pontieri et la., 1996).…”