L-DOPA-induced dyskinesia is a common side effect developed after chronic 
treatment with 3,4-dihydroxyphenyl-l-alanine (l-DOPA) in Parkinson's disease. 
The biological mechanisms behind this side effect are not fully comprehended 
although involvement of dopaminergic, serotonergic, and glutamatergic systems 
has been suggested. The present study utilizes in vivo amperometry to 
investigate the impact from unilateral 6-hydroxydopamine lesions and l-DOPA (4 
mg/kg, including benserazide 15 mg/kg) -induced dyskinetic behavior on striatal 
basal extracellular glutamate concentration and potassium-evoked glutamate 
release in urethane-anesthetized rats. Recordings were performed before and 
after local L-DOPA application in the striatum. In addition, effects from the 
5-HT(1A) receptor agonist (2R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin 
hydrobromide (8-OHDPAT; 1 mg/kg) was assessed on glutamate release and on 
dyskinetic behavior. The results revealed a bilateral ≈ 30% reduction of basal 
extracellular glutamate concentration and attenuated potassium-evoked glutamate 
release after a unilateral dopamine-depletion in L-DOPA naïve animals. In 
dyskinetic subjects, basal glutamate concentration was comparable to normal 
controls, although potassium-evoked glutamate release was reduced to similar 
levels as in drug naïve dopamine-lesioned animals. Furthermore, acute striatal 
L-DOPA administration attenuated glutamate release in all groups, except in the 
dopamine-lesioned striatum of dyskinetic animals. Co-administration of 8-OHDPAT 
and L-DOPA decreased dyskinesia in dopamine-lesioned animals, but did not affect 
potassium-evoked glutamate release, which was seen in normal animals. These 
findings indicate altered glutamate transmission upon dopamine-depletion and 
dyskinesia.