Pharmacological MRI mapping of age-associated changes in basal ganglia circuitry of awake rhesus monkeys

While the pathophysiological changes induced by the loss of dopamine innerv ation in the basal ganglia by Parkinson's disease (PD) are well studied, li ttle is, known about functional changes in the neural circuitry of this are a during normal aging. Here we report the first survey of age-associated ch anges in the basal ganglia of behaviorally characterized, awake rhesus monk eys, using pharmacological MRI to map responses to dopaminergic stimulation . Apomorphine, a mixed D-1/D-2 dopamine receptor agonist, evoked little cha nge in the substantia nigra (SN) of aged animals while significantly reduci ng activation in young adult I monkeys. Compared to young animals, both apo morphine and D-amphetamine (which increases synaptic dopamine levels) signi ficantly increased activation of the aged rhesus globus pallidus externa (G Pe). In addition, the aged animals showed decreased activity in the putamen in response to D-amphetamine administration. Although the responses in the SN and putamen of the aged monkeys differed from those in animal models of PD, the apomorphine-evoked activation i of their GPe corresponded with apo morphine-induced increases in neuronal activity seen in Parkinson's patient s and animal models. Given the major role of the GPe in regulating motor be havior, the altered responses in the aged GPe may contribute significantly to the motor slowing and movement dysfunctions characterizing advanced age. (C) 2001 Academic Press.