Microdialysis in Parkinsonian Patient Basal Ganglia: Acute Apomorphine-Induced Clinical and Electrophysiological Effects Not Paralleled by Changes in the Release of Neuroactive Amino Acids Ernesto Fedele,* Paolo Mazzone,† Alessandro Stefani,‡ , § Andrea Bassi,§ Maria Antonia Ansaldo,* Maurizio Raiteri,* Maria Grazia Altibrandi,† Mariangela Pierantozzi,‡ , § Patrizia Giacomini, ¶ Giorgio Bernardi,‡ , § and Paolo Stanzione‡ , § *Dipartimento di Medicina Sperimentale, Sezione di Farmacologia e Tossicologia, Viale Cembrano 4, 16148 Genova, Italy; †Divisione di Neurochirurgia, Ospedale CTO, Via S. Nemesio 21, 00146 Rome, Italy; ‡Dipartimento di Neuroscienze, Universita ` di Roma “Tor Vergata,” Via di Tor Vergata 135, 00133 Rome, Italy; §IRCCSS Clinica Santa Lucia, Via Ardeatina 306, 00179 Rome, Italy; and ¶ Istituto di Clinica delle Malattie Nervose e Mentali, Universita ` di Roma “La Sapienza,” Via dell’Universita ` 30, 00185 Rome, Italy Received March 24, 2000; accepted September 26, 2000; published online December 27, 2000 During stereotaxic neurosurgery for deep brain stimulation in Parkinson’s disease (PD), we performed a microdialysis study of the extracellular amino acid (aspartate, glutamate, glycine, and GABA) concentra- tions. Their levels were measured in the GPe/GPi of five and in the STN of four different PD patients, after prolonged therapy washout. The results show stable values of basal release of the examined amino acids within 1 h. The basal levels of GABA in “OFF” state were significantly higher in the GPi than in the GPe. Acute apomorphine administration, while induc- ing clinical amelioration and electrophysiological changes in the examined nuclei, did not change amino acid concentrations. This result could be related to a limited microdialysis ability to detect subtle changes in amino acid spontaneous release. Alternatively, it could suggest that dopaminergic receptors located in the output nuclei, possibly present also in humans, might mediate the acute apomorphine clinical effects, not involving amino acid changes along the direct and/or indirect pathway. © 2001 Academic Press Key Words: Parkinson’s disease; microdialysis; apo- morphine; endogenous amino acids; basal ganglia; neurosurgery; electrophysiology. INTRODUCTION Since the late 1980s (1, 13), it has been proposed that alterations between excitatory and inhibitory neuro- transmission in the internal globus pallidus/substantia nigra pars reticulata (GPi/SNr), produced by the un- balance between the “direct” and “indirect” pathways, play a crucial role in Parkinson’s disease (PD) physio- pathology (29). Levodopa therapy may restore this un- balance. However, the late complications of levodopa therapy did produce a renovated interest in stereotaxic surgery (27). In order to eliminate the surgical risks related to tissue lesioning, a novel surgical approach, called deep brain stimulation (DBS), has been devel- oped based on the insertion of permanent electrodes into the brain through which a high-frequency stimu- lation (HFS) is applied by means of a subcutaneous stimulator (3). The need of a correct target identification induced most of the neurosurgical groups to use extracellular recordings in multibarrel x-shaped electrode arrange- ment to explore the functional activity around the se- lected area with extracellular recordings (18 –20, 32, 50). Several electrophysiological and clinical data, ob- tained during stereotaxic surgery for DBS electrode implantation, show that acute administration of apo- morphine causes a significant decrease in the cell firing activity of GPi neurons (19, 48, 49) paralleled by ame- lioration of PD hypokinesia as assessed by intraopera- tive UPDRS scale (14). Moreover, resting activity of cells in the subthalamic nucleus (STN) appears to be high in PD patients resembling those recorded in MPTP-treated monkey (20). All these alterations might be ascribed to the unbalance between GABA and glutamate in the basal ganglia (BG) output nuclei men- tioned above (1, 13). To verify this hypothesis, micro- dialysis measurements of neurotransmitter release from BG nuclei, as external globus pallidus (GPe)/GPi and STN, could be crucial. Some years ago, a microdialysis study was per- formed during stereotaxic thalamic surgery for PD tremor with the aim to test the reliability of this tech- nique for neurochemical characterization of the target area (36). Microdialysis probes were inserted in the same trajectory as the electrodes thus avoiding addi- tional damage to the tissue. Experimental Neurology 167, 356 –365 (2001) doi:10.1006/exnr.2000.7568, available online at http://www.idealibrary.com on 356 0014-4886/01 $35.00 Copyright © 2001 by Academic Press All rights of reproduction in any form reserved.