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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.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10677628&dopt=Abstract
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Psychiatry Res. 1998 May 8;78(3):163-72.
Platelet serotonergic functions and light therapy in seasonal affective disorder.
Stain-Malmgren R, Kjellman BF, Aberg-Wistedt A.
Department of Psychiatry, Institution of Clinical Science, Karolinska Institute, St. Goran's Hospital, Stockholm, Sweden.
We investigated platelet 14C-serotonin uptake and platelet [3H]LSD and [3H]paroxetine binding in 11 patients with seasonal affective disorder (SAD). Patients were reinvestigated after light therapy, applied at 07.00-09.00 h for 10 consecutive days. The degree of depression was rated before and after light therapy using the Comprehensive Psychopathological Rating Scale (CPRS). Baseline data in patients were compared with data from a control group consisting of 11 age- and sex-matched healthy volunteers. Seven patients responded to light therapy with a > 50% reduction in CPRS scores. In non-responders, the reduction in CPRS was 24.7 +/- 5.5%. There was a significant inverse correlation (P = 0.014) between Km for platelet 14C-serotonin uptake and CPRS scores. Patients had significantly higher Bmax for platelet [3H]LSD binding (P = 0.04) and significantly lower Bmax for platelet [3H]paroxetine binding (P = 0.016). There was a strong, multiple correlation between Bmax for [3H]LSD, as the dependent variable, and Km, Vmax and Bmax for [3H]paroxetine binding in patients (P < 0.0001) but not in controls. Responders to light therapy had significantly higher Km (P = 0.023) and significantly lower Bmax for [3H]paroxetine binding (P = 0.028) than non-responders. Bmax for [3H]paroxetine binding increased significantly to normal levels after light therapy. The results indicate that SAD is associated with aberrations in the serotonin uptake mechanism. The enhanced 5-HT2-receptor density may reflect a consequential up-regulation.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9657420&dopt=Abstract
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J ECT. 1998 Mar;14(1):15-24.
Increased platelet 5-HT2 receptor binding after electroconvulsive therapy in depression.
Stain-Malmgren R, Tham A, Aberg-Wistedt A.
Department of Clinical Neuroscience, Karolinska Institute, St. Gorans Hospital, Stockholm, Sweden.
We investigated the effect of electroconvulsive treatment (ECT) on platelet 14C-serotonin uptake, 3H-paroxetine binding and 5-HT2 receptors in 12 patients (10 women and 2 men) unresponsive to pharmacological treatment. The mean numbers of ECTs given was 6.1 +/- 1.5. Mean treatment days was 14.6 +/- 3.8. Mean percent reduction in MADRS scores was 80.7 +/- 19.7 (p < 0.002). The number of 5-HT2 receptors increased significantly and uniformly after ECT (p = 0.011). There was no correlation between the degree of increase in 5-HT2 receptor densities and the reduction in MADRS scores after ECT. There was no difference in mean Bmax for platelet 3H-paroxetine binding before and after ECT. Bmax increased in six patients and decreased in six patients. The study shows an increase in platelet 5-HT2-receptor densities in depression after repeated ECT. Recognizing the similarities between 5-HT2 receptors in platelets and cerebral cortex, it seems reasonable to assume that a similar upregulation of cortical 5-HT2 receptors occurs after ECT.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9661089&dopt=Abstract
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