Decrease in human striatal dopamine D2 receptor density with age: a PET study with [11C]raclopride

Area of Science:

• Neuroscience
• Radiochemistry
• Gerontology

Background:

• Dopamine D2 receptors are crucial for motor control and cognitive functions.
• The aging process is associated with changes in neurotransmitter systems, including dopaminergic pathways.
• Understanding age-related alterations in dopamine D2 receptors is vital for explaining motor deficits in aging.

Purpose of the Study:

• To investigate the effect of age on the density and binding characteristics of striatal dopamine D2 receptors in healthy human subjects.
• To quantify the relationship between age and the maximal number of dopamine D2 receptors (Bmax) and their dissociation constant (Kd).

Main Methods:

• Positron Emission Tomography (PET) imaging was employed using the radioligand [11C]raclopride.
• Twenty-one healthy volunteers across a wide age range (20-81 years) participated in the study.
• Scatchard analysis was used to calculate Bmax and Kd from equilibrium PET scan data with varying radioligand specific activities.

Main Results:

• A significant age-dependent decline in the Bmax of striatal dopamine D2 receptors was observed (r = -0.49; p = 0.02).
• The dissociation constant (Kd) for dopamine D2 receptors remained unchanged with age.
• This indicates a loss in the number of available D2 receptors rather than a change in their binding affinity.

Conclusions:

• The human brain experiences an age-related reduction in the number of striatal dopamine D2 receptors.
• This decrease in dopamine D2 receptor density may contribute to age-associated changes in motor function and extrapyramidal symptoms.
• Further research into the nigrostriatal dopaminergic system's aging process is warranted.