Functional MRI of apomorphine activation of the basal ganglia in awake rhesus monkeys

Abstract

Functional magnetic resonance imaging (fMRI) was used to analyze blood oxygen level-dependent (BOLD) responses in the nigrostriatal system (caudate nucleus, putamen and substantia nigra) of awake rhesus monkeys to systemic apomorphine administration. The study (1) measured BOLD responses as an index of neuronal activity in the three structures following injections of the mixed D1/D2 agonist, and (2) assessed the effects of isoflurane anesthesia on the fMRI responses. Compared to control saline injections, 0.1 mg/kg apomorphine significantly activated the caudate nucleus (P < or = 0.005), putamen (P < or = 0.001) and substantia nigra (P < or = 0.005). The responses were consistent with activation of GABAergic neurons in these three structures seen in other animal models. Isoflurane gas measurably blunted the response to apomorphine, so that a significant apomorphine activation was only seen in the substantia nigra of anesthetized animals. Even there, the mean MR signal change was reduced from 9.8% in awake monkeys to 2.3% in anesthetized animals. The data support the hypothesis that fMRI can be used to study the effects of drugs that alter basal ganglia activity in awake rhesus monkeys.