Aging regulates 5-HT(1B) receptors and serotonin reuptake sites in the SCN

Middle age is associated with changes in circadian rhythms (e.g., alterations in the timing of the circadian wheel running rhythm) which resemble changes induced by selective destruction of the serotonergic input to the suprachiasmatic nucleus (SCN), the principal mammalian circadian pacemaker. We hypothesized that serotonergic neurotransmission in the SCN is decreased in middle-aged hamsters, as compared to young adults. This hypothesis was tested indirectly by investigating the effect of aging on two markers of serotonin neurotransmission, 5-HT(1B) receptors and serotonin reuptake sites, which are regulated by serotonin. Previous studies have shown that experimentally induced decreases in serotonergic neurotransmission increase 5-HT(1B) receptors but decrease serotonin reuptake sites. Quantitative autoradiography was conducted using [125I]iodocyanopindolol ([125I]ICYP) and [3H]paroxetine, selective radioligands for the 5-HT(1B) receptors and the serotonin reuptake sites, respectively. Consistent with the hypothesis, specific ([125I]ICYP binding was significantly elevated in the SCN of middle-aged hamsters, as compared to young hamsters. The results also showed that serotonin reuptake sites in the SCN were significantly increased in both middle-aged and old hamsters, as compared to young controls. This result could not have been caused by decreased serotonin release. Alternatively, increased serotonin reuptake, which would reduce serotonin levels in the synaptic cleft, may cause or contribute to the increase in 5-HT(1B) receptor binding in the SCN in middle aged animals. These results show that the SCN exhibits changes in serotonergic function during middle age, which has been characterized by changes in the expression of circadian rhythms. Because these changes occur during middle age, they probably reflect the aging process, rather than senescence or disease.