Serotonin 5-HT1A Receptor Binding Potential Declines with Age as Measured by [11C]WAY-100635 and PET

Abstract

Positron emission tomography (PET)

Prenatal Exposure to Maternal Cigarette Smoking and the Adolescent Cerebral Cortex

“…These are but two examples of sex-specific effects of prenatal exposure to nicotine that may translate into long-lasting morphological changes in serotonin-rich regions. One such region is the OFC (Tork, 1990;Dillon et al, 1991;Marutle et al, 2001;Tauscher et al, 2001) and this is where we found significant effects of PEMCS on cortical thickness in the female adolescents. In general, thickness of a cortical region, as estimated from MRI, most likely reflects the volume of various cellular compartments constituting the cortex (axons (29%), dendrites (30%), cell bodies and vessels (14%), and glia (10%) percentages based on the mouse cerebral cortex) and the effect of the adjacent white matter (Braitenberg, 2001; Figure 1 Surface maps of statistical significance of PEMCS on cortical thickness.…”

Parametric and Regional Maps of Free Serotonin 5HT1A Receptor Sites in Human Brain as Function of Age in Healthy Humans

“…One study demonstrated an association with age in young and aged monkeys with decrease of binding to receptors in temporal and frontal cortices in the elderly monkeys, but less displacement of [ 11 C]WAY binding after injection of the agonist 8-OH-DPAT, suggesting impaired affinity in the aged monkeys (Tsukada et al, 2001). One study of humans subjects aged 22-53 years found a 10% decline per decade of pB in the whole brain, except in mesiotemporal cortex (Tauscher et al, 2001), and one other study of a wider age range of human subjects (21-80 years) found significant decrease in receptor-rich areas of the brain, but only in men. A more recent study on previously depressed subjects reported a decrease with age in 5HT 1A receptor binding compared to controls in both raphé nuclei and postsynaptic regions (Bhagwagar et al, 2004).…”

“…The evidence for an effect of normal aging on the availability of [ 11 C]WAY-binding sites is equivocal. Thus, normal aging showed significant decline of cortical [ 11 C]WAY binding in one study of rhesus monkeys (Tsukada et al, 2001) and three studies of humans (Tauscher et al, 2001;Cidis Meltzer et al, 2001;Bhagwagar et al, 2004), where as no correlation with age was reported in two other studies of humans (Parsey et al, 2002;Rabiner et al, 2002). In addition, the findings may reflect problems with kinetic analysis of binding due to the very rapid metabolism of the tracer in the circulation (Gunn et al, 1998;Osman et al, 1998) and the reported high inter-subject variability in [ 11 C]WAY binding, as demonstrated in a large cohort of healthy male subjects.…”

Age and sex effects on 5-HT4 receptors in the human brain: A [11C]SB207145 PET study

“…A decline with age is described for the 5-HT 1A receptors in both genders (Moller et al, 2007;Tauscher et al, 2001), in women only (Costes et al, 2005) and men only (Cidis Meltzer et al, 2001;Rabiner et al, 2002). Studies involving the serotonin transporter have described localized decreases with age in varying regions (Kalbitzer et al, 2009;Meyer et al, 2001;Reimold et al, 2008).…”