Subchronic administration of L-DOPA to adult rats with a unilateral 6-hydroxydopamine lesion of dopamine neurons results in a sensitization of enhanced GABA release in the substantia nigra, pars reticulata.
L-DOPA is the most effective pharmacological agent used for the symptomatic treatment of Parkinson's disease but long-term L-DOPA treatment induces involuntary abnormal movements such as dyskinesias. The present study, using in vivo microdialysis, investigated the effects of a single or subchronic administration of L-DOPA to adult rats with a unilateral 6-OHDA lesion of dopamine neurons on GABA release in the substantia nigra, pars reticulata (SNr). The results indicate that a challenge injection of L-DOPA (50 mg/kg, i.p.) significantly increases GABA levels in the SNr of rats treated with a daily repeated administration of L-DOPA (50 mg/kg, i.p.). Further statistical analysis between groups also showed that extracellular GABA levels were significantly higher in the subchronic L-DOPA group than in the group receiving only one injection of L-DOPA. These results show that the subchronic administration of L-DOPA results in a sensitization of enhanced extracellular GABA levels in the SNr.
Yamamoto
Noriko
N
Department of Anatomy and Neurobiology, Boston University School of Medicine, 715 Albany Street, Room L1001, Boston, MA 02118, USA.
Pierce
R Christopher
RC
Soghomonian
Jean-Jacques
JJ
D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D007980:Levodopa / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000378:metabolism; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism*
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D007980:Levodopa; D005680:gamma-Aminobutyric Acid; D016627:Oxidopamine; D004298:Dopamine