Localization of 5-HT7 receptors in rat brain by immunocytochemistry, in situ hybridization, and agonist stimulated cFos expression

5-HT7 receptors are recently identified members of the seratonin receptor f amily that have moderate to high affinity for several important psychotropi c drugs. However, the lack of selective ligands has impeded the study of th e brain distribution of these receptors. In this report, we describe the lo calization of 5-HT7 receptor in rat forebrain by immunocytochemistry, in si tu hybridization of 5-HT7 mRNA, and functional stimulation of cFOS expressi on by 5-HT7 receptor activation. The anatomical localization of 5-HT7 mRNA in situ hybridization signal. Prominent immunostaining was apparent in nume rous sites within the cerebral cortex, hippocampal formation, tenia tecta, thalamus and hypothalamus. 5-HT7 receptors were detected in suprachiasmatic nucleus by both immunocytochemistry and in situ hybridization. At a micros copic level, both cell bodies and proximal fibers were strongly stained in these regions, suggesting a somatodendritic subcellular distribution. 5-HT7 receptor-like immunoreactivity was further compared with 5-HT7 mediated bi ological function by administering 8-OH-DPAT intracerebroventricular inject ion (icv) with WAY 100135 (to block 5-HT1A receptors) followed by double im munostaining localization of cFos activation and 5-HT7 receptors. In all re gions examined, cFos stimulation and 5-HT7-like immunoreactivity colocalize d to the same neurons. Furthermore, cFos activation by 8-OH-DPAT was blocke d by pimozide - a 5-HT7 antagonist. Therefore, by using multiple strategies , we were able to localize 5-HT7 receptors in rat brain unequivocally. The distribution of these receptors is consistent with their involvement in the control of circadian activity and the action of anti-depressants and atypi cal neuroleptics. (C) 2001 Elsevier Science B.V. All rights reserved.