The motor signs of
Parkinson's disease have been partly attributed to an overinhibition of the external globus pallidus (GP) that results from hyperactivity of striatopallidal
GABA/enkephalinergic neurons. The goals of this study were to measure basal levels of extracellular fluid
GABA in the GP of normal cats,
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (
MPTP)-treated parkinsonian cats and cats spontaneously recovered from
MPTP-induced parkinsonism, and to examine the effects of
opioid receptor activation on
potassium (K+)-evoked
GABA release in the GP in these animals. Basal GP
GABA levels were increased 75% from normal in parkinsonian animals 1 week after
MPTP administration and returned to control levels in recovered animals 6 weeks after
MPTP administration. No significant differences were observed in K+-evoked
GABA release across conditions. The
opioid receptor agonist [D-Ala2]-
Met-Enkephalinamide (
DALA) significantly attenuated K+-evoked
GABA release in the GP of
MPTP-treated symptomatic and recovered cats, but had no significant effect on
GABA release in normal animals. These data show that basal GP
GABA levels are elevated coincident with expression of parkinsonian signs and return to normal in animals that have functionally compensated for a nigrostriatal lesion.
DALA-induced inhibition of pallidal
GABA release after a
dopamine-depleting lesion, suggests that
enkephalin may attenuate
GABA release in the GP specifically after striatal
dopamine loss.