GABA-opioid interactions in the globus pallidus: [D-Ala2]-Met-enkephalinamide attenuates potassium-evoked GABA release after nigrostriatal lesion.
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.
Schroeder
J A
JA
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Schneider
J S
JS
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002415:Cats; D004195:Disease Models, Animal; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology*; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D005917:Globus Pallidus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D020127:Recovery of Function; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000378:metabolism*
D009292:Narcotic Antagonists; D009270:Naloxone; D005680:gamma-Aminobutyric Acid; D004744:Enkephalin, Methionine; C022118:enkephalinamide-Met, Ala(2)-; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D011188:Potassium