Aging regulates 5-HT1B receptors and serotonin reuptake sites in the SCN

Middle age is associated with changes in circadian rhythms (e.g., alteratio ns in the timing of the circadian wheel running rhythm) which resemble chan ges induced by selective destruction of the serotonergic input to the supra chiasmatic nucleus (SCN), the principal mammalian circadian pacemaker. We h ypothesized that serotonergic neurotransmission in the SCN is decreased in middle-aged hamsters, as compared to young adults. This hypothesis was test ed indirectly by investigating the effect of aging on two markers of seroto nin neurotransmission, 5-HT1B receptors and serotonin reuptake sites, which are regulated by serotonin. Previous studies have shown that experimentall y induced decreases in serotonergic neurotransmission increase 5-HT1B recep tors but decrease serotonin reuptake sites. Quantitative autoradiography wa s conducted using [I-125]iodocyanopindolol ([I-125]ICYP) and [H-3]paroxetin e, selective radioligands for the 5-HT1B receptors and the serotonin reupta ke sites, respectively. Consistent with the hypothesis, specific ([I-125]IC YP binding was significantly elevated in the SCN of middle-aged hamsters, a s compared to young hamsters. The results also showed that serotonin reupta ke sites in the SCN were significantly increased in both middle-aged and ol d hamsters, as compared to young controls. This result could not have been caused by decreased serotonin release. Alternatively, increased serotonin r euptake, which would reduce serotonin levels in the synaptic cleft, may cau se or contribute to the increase in 5-HT1B receptor binding in the SCN in m iddle aged animals. These results show that the SCN exhibits changes in ser otonergic function during middle age, which has been characterized by chang es in the expression of circadian rhythms. Because these changes occur duri ng middle age, they probably reflect the aging process, rather than senesce nce or disease. (C) 2000 Elsevier Science B.V. All rights reserved.