Adenosine A(2A) receptors (A(2A)R) have received increasing attention for the treatment of
L-DOPA-induced
dyskinesias in
Parkinson disease. In the present study, A(2A)R
messenger RNA (
mRNA) and receptor-specific binding in the brain of
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (
MPTP) monkeys were studied
after treatment with
L-DOPA and a selective NR1A/2B
NMDA receptor antagonist,
CI-1041. Four
MPTP monkeys received
L-DOPA/
benserazide and all developed
dyskinesias, whereas among the four
MPTP monkeys who additionally received
CI-1041, only one developed mild
dyskinesias. Four normal monkeys and four
MPTP-treated monkeys were also studied. All
MPTP monkeys had similar striatal
dopamine (DA)
denervation. A(2A)R
mRNA levels, measured by in situ hybridization, were increased in the rostral lateral caudate and putamen of saline-treated
MPTP monkeys as well as in the caudal lateral and medial putamen when compared with those of controls. A(2A)R
mRNA levels remained elevated in the rostral caudate and putamen of
L-DOPA-treated
MPTP monkeys when compared with those of controls. A(2A)R
mRNA levels of
L-DOPA + CI-1041-treated monkeys were at control levels and decreased in the lateral rostral caudate and caudal putamen when compared with those of
L-DOPA-treated and saline-treated
MPTP monkeys respectively. No change was measured in the caudal medial putamen and caudate nucleus. A(2A)Rs labeled by autoradiography with [(3)H]
SCH-58261 had lower level in the
L-DOPA + CI-1041-treated
MPTP monkeys compared with saline- or
L-DOPA-treated
MPTP and control monkeys in the rostral lateral and medial caudate and the putamen. No effect of lesion or
L-DOPA treatment was measured on [(3)H]
SCH-58261-specific binding. These findings suggest that blockade of
NMDA receptors could prevent the development of
dyskinesias by altering A(2A)Rs.