Time of day but not aging regulates 5-HT7 receptor binding sites in the hamster hippocampus

Activation of 5-HT7 receptors influences memory as well as circadian rhythms and other processes. This study investigated the regulation of the 5-HT7 receptors in the hippocampus, a likely substrate for the effects of 5-HT7 receptor compounds on memory. Because endogenous serotonin release is higher during the active phase, and chronic treatment with a serotonin-selective reuptake inhibitor down-regulates 5-HT7 receptors, we hypothesized that 5-HT7 receptors exhibit 24-h variations. We also hypothesized that aging decreases 5-HT7 receptors in the hippocampus, as it does in the dorsal raphe nucleus, a brain site for serotonergic resetting of circadian rhythms. Male hamsters (young, 3-5 mos; old, 17-21 mos) exposed to a light:dark cycle were euthanized at 4 times of day (zeitgeber times [ZT]1, 6, 13, & 19; ZT12 = time of lights:off). 5-HT7 receptor autoradiography was conducted on hippocampal sections using [3H]8-OH-DPAT [2 nM] as the radioligand and SB-269970 [1 μM] to define nonspecific binding. Slide-mounted sections and radioactive standards were apposed to X-ray films; the resultant autoradiograms were assessed by computer-assisted microdensitometry. Specific 5-HT7 receptor binding was robustly expressed in the dentate gyrus (DG) and CA1 but not in the CA2 or CA3. In the CA1 and DG, specific 5-HT7 receptor binding exhibited 24-h rhythms with troughs at night (P < 0.005; P < 0.05, respectively). Aging did not significantly affect specific 5-HT7 receptor binding in these regions, nor were significant time and age interactions observed. These findings suggest that the therapeutic effectiveness of 5-HT7 drugs may vary with time of day of administration but not with the age of the recipient.