Rapid and differential losses of in vivo dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) radioligand binding in MPTP-treated mice
Mr. Kilbourn et al., Rapid and differential losses of in vivo dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) radioligand binding in MPTP-treated mice, SYNAPSE, 35(4), 2000, pp. 250-255
The dose- and time-dependent changes of in vivo radioligand binding to the
neuronal membrane dopamine transporter (DAT) and vesicular monoamine transp
orter type 2 (VMAT2) were examined in mouse brain after MPTP( 1-methyl-4-ph
enyl-1,2,3,6-tetrahydropyridine) administrations. Regional brain distributi
on studies were done in male C57BL/6 mice using simultaneous injections of
d-threo-[H-3]methylphenidate (DAT) and (+)-alpha-[C-11]dihydrotetrabenazine
(VMAT2). Single (55 mg/kg i.p.) or multiple (4 x 10 mg/kg i.p., I-hour int
ervals) administration of MPTP caused significant reductions in [3H]methylp
henidate and [C-11] dihydrotetrabenazine specific striatal binding, measure
d 14 days later. The single high dose of MPTP produced greater losses of [C
-11]dihydrotetrabenazine binding than did the multiple MPTP dosing regimen.
Using the single high dose of R MPTP, changes of in vivo binding of the tw
o radioligands were determined at 1, 3, and 14 days after neurotoxin inject
ion. At 1 day, there are large losses of [H-3] methylphenidate binding (DAT
) but no changes in [C-11] dihydrotetrabenazine binding to the VMAT2 site i
n the striatum. At 3 and 14 days, there were >50% losses of binding of both
bot radioligands, but significantly (P < 0.001) greater losses of VMAT2 bi
nding of [11C]dihydrotetrabenazine. These studies indicate that the losses
of the neuronal membrane and vesicular transporters are not always equal, a
nd do not occur in the same time frame? after administration of the neuroto
xin MPTP. (C) 2000 Wiley-Liss, Inc.