Clinical and electrophysiological effects of apomorphine in Parkinson's disease patients are not paralleled by amino acid release changes: a microdialysis study.
We performed a microdialysis investigation of extracellular amino acid (glutamate and GABA) concentrations during sterotaxic neurosurgery (the implantation of permanent electrodes in the internal globus pallidus (GPi) or subthalamic nucleus (STN) for deep brain stimulation in advanced Parkinson's disease (PD) patients, after prolonged therapy wash-out). Electrophysiological single unit recordings and perioperative clinical status assessments were also performed. Amino acid levels were measured in the GPi and GPe (external globus pallidus) of three PD patients and in the STN of another three PD patients. Stable basal release values of the examined amino acids were obtained within one hour. In clinical "off" state, the basal levels of GABA in the GPi were double those in the GPe in all the three patients. This finding could represent a biochemical marker for GPi target identification in PD surgery. Acute subcutaneous apomorphine administration induced electrophysiological changes and clinical amelioration but did not change amino acid concentrations. This result could be due to methodological limitations of the microdialysis technique. Alternatively, it could suggest that the clinical effects of acute apomorphine might also be mediated by direct activation of dopaminergic receptors located in the output nuclei.
Fedele
E
E
Department of Experimental Medicine, Section of Pharmacology and Toxicology, University of Genoa. fedele@pharmatox.unige.it
Stefani
A
A
Bassi
A
A
Pepicelli
O
O
Altibrandi
M G
MG
Frasca
S
S
Giacomini
P
P
Stanzione
P
P
Mazzone
P
P
D000368:Aged; D000596:Amino Acids / Q000378:metabolism*; D001058:Apomorphine / Q000008:administration & dosage* / Q000009:adverse effects; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D001931:Brain Mapping; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D005917:Globus Pallidus / Q000187:drug effects / Q000503:physiopathology; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D009460:Neurologic Examination / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D020531:Subthalamic Nucleus / Q000187:drug effects / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D001058:Apomorphine