Decrease in Human Striatal Dopamine D₂ Receptor Density with Age: A PET Study with [¹¹C]Raclopride

Abstract

The effect of age on human striatal dopamine D2 receptors was investigated with positron emission tomography (PET) using [11C]raclopride as a radioligand. Twenty-one healthy volunteers aged from 20 to 81 years were studied. An equilibrium method was applied and two separate PET scans with different specific activities of [11C]raclopride were performed. The maximal number of receptors (Bmax) and their dissociation constant (Kd) were calculated using Scatchard analysis. There was an age-dependent decline in the Bmax (r = -0.49; p = 0.02) of striatal D2 receptors while the Kd remained unchanged. The results show that there is an age-related loss of striatal D2 receptors, which, together with other changes in the brain nigrostriatal dopaminergic system, may contribute to extrapyramidal symptoms associated with aging.

Dopamine reuptake site densities in patients with social phobia

“…Our data indicate that dopamine reuptake site density decreases about 5% every 10 years among the oldest subjects (over 50 years) as they get older, and this is in line with the findings on D 2 receptor densities (28). It is quite possible that decreased dopamine transmission may have a role in depression among older people, and recent results indicate that the MAO-B inhibitor selegiline in high doses is effective for therapy-resistant depression in older patients (29).…”

A study of performance on tests from the CANTAB battery sensitive to frontal lobe dysfunction in a large sample of normal volunteers: Implications for theories of executive functioning and cognitive aging

“…Overall, our findings are compatible with the results of studies using a variety of neuroimaging modalities that aging is especially associated with structural, metabolic, and neurochemical changes in regions of the prefrontal cortex (Pantano et al, 1984;Riege et al, 1985;Waldemar et al, 1991), the striatum (Murphy et al, 1992;Riege et al, 1985;Rinne et al, 1993;Sawle et al, 1990;van Dyck et al, 1995), and also the temporal lobes (Arrigada et al, 1992;Loessner et al, 1995;Pantano et al, 1984;Price et al, 1991). This position is not very different from that reached by West (1996), after a comprehensive review of the available neurobiological evidence.…”

Contribution of SPECT Measurements of D2and 5-HT2AOccupancy to the Clinical Development of the Antipsychotic SB-773812

“…Age-related differences between the healthy volunteer and patient groups might also account for the high D 2 occupancy variability. An approximately 5% decrease per decade in D 2 R availability above the age of 30 y has been reported (32). In our study, the mean age of the healthy volunteer group was lower than that of the patient groups (Table 1).…”