6‐[18F]fluoro‐L‐DOPA‐PETstudies show partial reversibility of long‐term effects of chronic amphetamine in monkeys

The acute and long‐term effects of chronic amphetamine administration on the striatal dopamine system in monkeys were assessed with 6‐[18F]fluoro‐L‐DOPA (FDOPA) and positron emission tomography (PET). Vervet monkeys (Cerecopithecus aethiops) were administered amphetamine doses, i.m., that increased from 4 mg/kg/d to 18 mg/kg/d over a 10 day period. Post‐amphetamine FDOPA‐PET scans at 1–2, 3–4, and 6 week time points in individual subjects showed persistent decrements in dopamine synthesis capacity as reflected by FDOPA influx rate constant (Ki) values being ∼30% that of pre‐drug assessment. In other animals that were administered the same drug regimen, biochemical analysis of striatal regions at 1–2 weeks post‐drug indicated that dopamine concentrations were decreased by ∼95% throughout caudate and putamen regions, while the homovanillic acid/dopamine level ratio was increased 3–10‐fold. Post‐drug FDOPA‐PET Ki values remained consistently low up to 6 weeks; however, at the 5–6 month time point, relative increases in FDOPA‐Ki values (∼53% of pre‐drug values) were observed for all subjects, indicative of partial recovery of striatal dopamine synthesis capacity.