I-125-CGP 64213 binding to GABA(B) receptors in the brain of monkeys: Effect of MPTP and dopaminomimetic treatments

Much evidence indicates that abnormal GABA neurotransmission may be implica ted in the pathophysiology of Parkinson's disease (PD) and dopaminomimetic- induced dyskinesias (DID). In this study, autoradiography using I-125-CGp 6 4213 was performed to investigate GABA(B) receptor density in the brain of control monkeys as web as monkeys with MPTP-induced nigrostriatal depletion . Three MPTP monkeys received pulsatile administrations of the D1 dopamine (DA) receptor agonist (SKF 82958) whereas a long-acting D2 DA receptor agon ist (cabergoline) was given to another three animals. SKF 82958 treatment r elieved parkinsonian symptoms but two of three animals developed DID. Caber goline induced a comparable motor benefit effect without persistent DID. I- 125-CGP 64213 binding to GABA(B) receptors was heterogeneous throughout the brain with the highest levels in the medial habenula of the thalamus. MPTP induced a decrease (-40%) of I-125-CGP 64213 binding to GABA, receptors in the substantia nigra pars compacta (SNpc) and an increase (+29%) in the in ternal segment of the globus pallidus (GPi). This increase in the GPi was n ot affected by SKF 82958 but partly reversed by cabergoline, No change was seen in the striatum, the thalamus, the external segment of the globus pall idus, and the substantia nigra pars reticulata following MPTP and dopaminom imetic treatments. The changes of GABA(B) receptors observed in the SNpc an d in the GPi suggest that alteration of GABA(B) receptors may play a role i n the pathophysiology of PD and DID. (C) 2000 Academic Press.