Evaluation of age-related changes in serotonin 5-HT₂ and dopamine D₂ receptor availability in healthy human subjects

We assessed the relation between serotonin 5-HT₂ receptor availability and aging and compared it with that for dopamine D₂ receptors on 19 healthy male volunteers (age range, 21-49 years) using positron emission tomography (PET) and F-18 N-methylspiperone (NMS). 5-HT₂ Receptor availability was obtained using the ratio of the distribution volume in the region of interest to that in the cerebellum ( B_max′ K_d′ + 1). 5-HT₂ Receptor measures were obtained in frontal and occipital cortices. D₂ receptor availability in striatum was measured using the "ratio index". 5-HT₂ Receptor availability decreased significantly with age. This effect was significantly more accentuated for 5-HT₂ receptor availability in the frontal (r = 0.92, p ≤ 0.0001) than in the occipital (r = 0.67, p ≤ 0.0016) cortex (df = l, p < 0.025). Dopamine D₂ receptors were also found to decrease significantly with age (r = 0.63, p ≤ 0.007). In a given subject, striatal D₂ receptor availability significantly correlated with 5-HT₂ receptor availability in the frontal (r = 0.51, p ≤ 0.035) but not in the occipital cortex. These results document a decline in 5-HT₂ and D₂ receptor availability with age and showed an association between frontal 5-HT₂ and striatal D₂ receptors.