title: Exendin-4 treatment enhances L-DOPA evoked release of striatal dopamine and decreases dyskinetic movements in the 6-hydoxydopamine lesioned rat.
abstract: OBJECTIVE
  To determine whether the glucagon-like 1 peptide analogue exendin-4 (EX-4) augments the neurochemical effects of a single L-DOPA treatment and whether EX-4 can decrease L-DOPA induced dyskinesias (LIDS).
  
  
  METHODS
  Rats were lesioned with 6-hydroxydopamine (6-OHDA) and 7 days later given EX-4 for 7 days. The following day, rats were given L-DOPA and extracellular dopamine was measured. The animals were then killed to determine tissue dopamine. To study LIDS, EX-4 and/or L-DOPA were co-administered daily, 7 days after 6-OHDA. LIDS were determined on Days 2, 4, 8, 12 and 16 prior to neurochemical assessment.
  
  
  RESULTS
  EX-4 reduced 6-OHDA induced damage. Acute effects of L-DOPA were potentiated by EX-4 in lesioned rats. Treatments with EX-4 caused a progressive reduction in LIDS.
  
  
  CONCLUSIONS
  EX-4 treatment potentiates the effects of a single dose of L-DOPA. This augmentation indicates that lower L-DOPA doses might be used to the same effect in patients. The reduction in LIDS suggests that co-treatment with EX-4 could allow the use of L-DOPA with fewer side-effects and possibly therefore allow earlier introduction of L-DOPA in the clinic.
authors.affiliation: Department of Pharmacology, The School of Pharmacy, UCL.
authors.forename: Amjad
authors.initials: A
authors.lastname: Abuirmeileh
authors.forename: Alexander
authors.initials: A
authors.lastname: Harkavyi
authors.forename: Nazir
authors.initials: N
authors.lastname: Rampersaud
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lever
authors.forename: John A
authors.initials: JA
authors.lastname: Tadross
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
authors.forename: Peter S
authors.initials: PS
authors.lastname: Whitton
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D004357:Drug Synergism; D020820:Dyskinesias / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives; D007980:Levodopa / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008116:Lizards; D008297:Male; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014688:Venoms / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D010455:Peptides; D014688:Venoms; D007980:Levodopa; D052216:Glucagon-Like Peptide 1; D016627:Oxidopamine; D000077270:Exenatide; D004298:Dopamine