Striatal dopaminergic metabolism is increased by deep brain stimulation of the subthalamic nucleus in 6-hydroxydopamine lesioned rats Wassilios Meissner a , Torsten Reum b , Gesine Paul a , Daniel Harnack a,b , Reinhard Sohr b , Rudolf Morgenstern b , Andreas Kupsch a, * a Department of Neurology, Charite  Campus Virchow-Klinikum, Humboldt-University Berlin, Augustenburger Platz 1, 13353 Berlin, Germany b Institute of Pharmacology and Toxicology, Charite  Campus Virchow-Klinikum, Humboldt-University Berlin, Augustenburger Platz 1, 13353 Berlin, Germany Received 24 February 2001; accepted 8 March 2001 Abstract Deep brain stimulation of the subthalamic nucleus is an established therapeutic strategy for patients with Parkinson's disease. Although the exact mechanisms of action remain unknown, it is noteworthy that dopaminergic medication can be markedly reduced after neurostimulation of the subthalamic nucleus. Previously, we have shown that deep brain stimulation of the subthalamic nucleus is followed by an increase of striatal extracellular dopamine metabolites in naive rats. In the present study we examined the effects of deep brain stimulation on striatal monoamine metabolism in the intrastriatal 6-hydroxydopamine rat model of Parkinson's disease. Deep brain stimulation of the subthalamic nucleus was followed by a delayed increase of extracellular 3,4-dihydroxyphenylacetic and homovanillic whereas dopamine levels were unchanged in stimulated rats and controls. Our results indicate that deep brain stimulation of the subtha- lamic nucleus affects signi®cantly striatal dopaminergic metabolism in 6-hydroxydopamine lesioned rats. q 2001 Else- vier Science Ireland Ltd. All rights reserved. Keywords: Parkinson's disease; Deep brain stimulation; Subthalamic nucleus; Striatum; Dopaminergic metabolism; Microdialysis Parkinson's disease (PD) is characterized by a progres- sive degeneration of nigral dopamine (DA) neurons [4]. Within the ®rst years of treatment, the major symptoms can be suf®ciently controlled by dopaminergic medication. However, long-term pharmacological treatment is compli- cated by the occurrence of dyskinesias and motor ¯uctua- tions. During the 10 years deep brain stimulation (DBS) has emerged as a new powerful therapeutic approach for the treatment of PD [1,9]. DBS of the subthalamic nucleus (STN) alleviates dramatically levodopa-sensitive symptoms such as rigidity, bradykinesia, tremor, and dyskinesias [1,9]. The major advantage of this technique comprises its rever- sibility and the individual postoperative adjustment of the stimulation parameters [18]. Furthermore, dopaminergic medication which is given to compensate the striatal DA de®cit in PD patients can be reduced up to 50% after STN±DBS [13]. However, the effect of DBS on striatal neurotransmission in PD is unclear. There are some previous data suggesting that electrical stimulation of the STN may in¯uence the nigral and striatal DA system [7,12]. In a recent study, using clinical stimulation parameters, we have shown, that STN±DBS produced an increase of striatal extracellular DA metabolism in naive rats [14]. The present study aimed at investigating the effects of STN±DBS after partial dopaminergic lesion using the striatal 6-hydroxydo- pamine (6-OHDA) rat model of PD [8,17]. After governmental permission the study was carried out on 6-OHDA lesioned anaesthetized male Wistar rats (Harlan-Winkelmann, Germany, weighing 230±240 g during 6-OHDA-lesion and 350±540 g during DBS). A partial unilateral four-point lesion of the left striatum was performed by stereotaxic injection of 6-OHDA as described previously [11]. Four weeks after the surgery suf®cient lesioning was tested through amphetamine (2 mg/kg intraperitoneally (i.p.); Sigma Chemical Co, St. Louis, MO, USA) induced rotational behavior. Only Neuroscience Letters 303 (2001) 165±168 0304-3940/01/$ - see front matter q 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S0304-3940(01)01758-X www.elsevier.com/locate/neulet * Corresponding author. Tel.: 149-30-450-560103; fax: 149-30- 450-560901. E-mail address: andreas.kupsch@charite.de (A. Kupsch).