Relationships of 5-hydroxytryptamine immunoreactive terminal-like varicosities to 5-hydroxytryptamine-2A receptor-immunoreactive neuronal processes in the rat forebrain

The distributions of 5-hydroxytryptamine (5-HT)-immunoreactive (IR) varicos ities and 5-hydroxytryptamine-2A receptor (5-HT2A)-IR neuronal structures i n the rat brain have previously been described individually. Using double l abeling immunocytochemistry, the relationships between 5-HT2A-IR and 5-HT-I R elements in the forebrain of male rats has been studied at the light micr oscopic level. In neocortical regions (frontal, parietal and retrosplenial cortex), the strongest 5-HT2A-IR was found in the apical dendrites of pyram idal cells in layers III-V, while 5-HT-IR terminal-like varicosities were p resent in all layers but most prominently in the outer layers. In other for ebrain regions, the olfactory bulb, the hippocampal formation, and the isla nds of Calleja and Calleja magna, localized discrepancies were present betw een the 5-HT2A-IR neuronal profiles and the 5-HT-IR terminal-like varicosit ies. Hardly any additional juxtapositions between the 5-HT2A-IR neuronal pr ofiles and 5-HT-IR terminallike varicosities were revealed when the intrane uronal level of 5-HT was increased by monoamine oxidase inhibitor pretreatm ent (nialamide, 250 mg/kg, 3 h). Thus, in most forebrain regions, there wer e overall few juxtapositions between 5-HT terminal-like varicosities and 5- HT2A-IR neuronal structures, This observation suggests that 5-HT2A receptor mediated 5-HT transmission in the rat forebrain is mainly a volume transmi ssion process mediated via short distance diffusion in the extra-cellular s pace. (C) 2001 Elsevier Science BN. All rights reserved.