Striatal Glutamate Release in l-DOPA-Induced Dyskinetic Animals

Abstract

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-HT1A 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.

Neuroprotective effects of levetiracetam target xCT in astrocytes in parkinsonian mice

“…Several studies reported that excess glutamate release or function may be involved in levodopa‐induced dyskinesia in PD (Nevalainen et al . ; Kelsey and Neville ; Rascol et al . ).…”

β‐asarone and levodopa co‐administration protects against 6‐hydroxydopamine‐induced damage in parkinsonian rat mesencephalon by regulating autophagy: down‐expression Beclin‐1 and light chain 3B and up‐expression P62

“…However, long‐term treatment with l ‐dopa and benserazide hydrochloride tablets could cause adverse symptoms, such as various types of motor and non‐motor responses (e.g. oscillations and drug‐induced dyskinesia, which is characterized by erratic involuntary movements and psychiatric symptoms) . In other words, the problem of adverse effects of l ‐dopa should be considered.…”

“…oscillations and druginduced dyskinesia, which is characterized by erratic involuntary movements and psychiatric symptoms). 5,6 In other words, the problem of adverse effects of L-dopa should be considered.…”

REAL-TIME IN VIVO NEUROTRANSMITTER MEASUREMENTS USING ENZYME-BASED CERAMIC MICROELECTRODE ARRAYS: WHAT WE HAVE LEARNED ABOUT GLUTAMATE SIGNALING

“…Recently, using MEA recordings we have shown that tonic (resting) and phasic (transient release) glutamate signals are dissociable events. For example, (Day et al, 2006;Quintero et al, 2007;Rutherford et al, 2007;Hascup et al, 2008;Thomas et al, 2009;Hascup et al, 2010;Hinzman et al, 2010;Stephens et al, 2010;Hascup et al, 2011b;Hascup et al, 2011a;Mattinson et al, 2011;Stephens et al, 2011;Hascup et al, 2012;Hinzman et al, 2012;Matveeva et al, 2012a;Matveeva et al, 2012b;Onifer et al, 2012;Thomas et al, 2012;Nevalainen et al, 2013); Microdialysis: (Ueda and Tsuru, 1995;Yang et al, 1995;Battaglia et al, 1997;Biggs et al, 1997;Timmerman et al, 1999;Reinstrup et al, 2000;Schulz et al, 2000;Giovannini et al, 2001;Segovia et al, 2001;Galvan et al, 2003;Cavus et al, 2005;Clinckers et al, 2005;Calcagno et al, 2006;Segovia et al, 2006;Ballini et al, 2008;Hernandez et al, 2008;Lupinsky et al, 2010;Slaney et al, 2011;Li et al, 2012;Vasylieva et al, 2013). initial MEA studies conducted in rats under anesthesia at various ages revealed that tonic levels of glutamate are often ...…”