Expression of 5-HT7 receptor mRNA in the hamster brain: effect of aging and association with calbindin-D28K expression.

Aging affects several processes modulated by the 5-HT(7) receptor subtype, including circadian rhythms, learning and memory, and depression. Previously, we showed that aging induces a decrease in the hamster dorsal raphe (DRN) in both 5-HT(7) receptor binding and circadian phase resetting responses to 8-OH-DPAT microinjection. To elucidate the mechanisms underlying the aging decrease in 5-HT(7) receptors, we investigated aging modulation of 5-HT(7) receptor mRNA expression in the DRN, brain regions afferent to the DRN, and brain regions regulating circadian rhythms or memory. In situ hybridization for 5-HT(7) receptor mRNA was performed on coronal sections prepared from the brains of young, middle-aged, and old male Syrian hamsters. 5-HT(7) receptor mRNA expression was quantified by densitometry of X-ray film autoradiograms. The results showed that aging did not significantly affect 5-HT(7) receptor mRNA expression in the DRN or most other brain regions examined, with the exception of the cingulate cortex and paraventricular thalamic nucleus. Within the suprachiasmatic nucleus, the site of the master circadian pacemaker in mammals, 5-HT(7) receptor mRNA expression was localized in a discrete subregion resembling the calbindin subnucleus previously described. A second experiment using adjacent tissue sections showed that 5-HT(7) receptor mRNA and calbindin mRNAs were concentrated in the same region of the SCN, and as well as in the same region of several other brain structures. The localization of 5-HT(7) receptors and calbindin mRNAs within the same regions suggests that the proteins they encode may interact to modulate processes such as circadian timekeeping.