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 family that have moderate to high affinity for several important psychotropic drugs. However, the lack of selective ligands has impeded the study of the brain distribution of these receptors. In this report, we describe the localization of 5-HT7 receptor in rat forebrain by immunocytochemistry, in situ hybridization of 5-HT7 mRNA, and functional stimulation of cFOS expression by 5-HT7 receptor activation. The anatomical localization of 5-HT7 mRNA in situ hybridization signal. Prominent immunostaining was apparent in numerous 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 microscopic 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 biological function by administering 8-OH-DPAT intracerebroventricular injection (icv) with WAY 100135 (to block 5-HT1A receptors) followed by double immunostaining localization of cFos activation and 5-HT7 receptors. In all regions examined, cFos stimulation and 5-HT7-like immunoreactivity colocalized to the same neurons. Furthermore, cFos activation by 8-OH-DPAT was blocked 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 atypical neuroleptics. (C) 2001 Elsevier Science B.V. All rights reserved.