EFFECTS OF DOPAMINERGIC DRUG TREATMENTS ON IN-VIVO RADIOLIGAND BINDING TO BRAIN VESICULAR MONOAMINE TRANSPORTERS

The effects of various dopaminergic drug treatments on the in vivo reg ional brain distribution of high affinity radioligands ([C-11]dihydrot etrabenazine and [C-11]methoxytetrabenazine) for the rat brain vesicul ar monoamine transporter (VMAT2) were determined. Acute treatments wit h reserpine (2 mg/kg i.p.), tetrabenazine (10 mg/kg i.v.) or related b enzoisoquinolines significantly reduced radiotracer binding in vivo. I n contrast, radiotracer distributions remained unchanged after treatme nts with other dopaminergic drugs, whether given by single injection ( haloperidol, 1 mg/kg i.p., pargyline 80 mg/kg), repeatedly (pargyline, 80 mg/kg s.c,, 14 days), or by continuous infusion (deprenyl, 10 mg/k g/day, 5 days; L-DOPA methyl ester 100 mg/kg/day, 5 days). Repeated in jections of tetrabenazine (5 mg/kg i.p., twice daily, 3 days) did not alter in vivo radioligand binding measured after allowing drug washout from the brain. These studies support the proposal that in vivo PET i maging of VMAT2 radioligands in patients with extrapyramidal movement disorders will not be affected by concurrent use of L-DOPA or deprenyl .