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Exp Brain Res (2008) 185:497507 DOI 10.1007/s00221-007-1171-1
RESEARCH ARTICLE
High frequency stimulation of the subthalamic nucleus modulates neurotransmission in limbic brain regions of the rat
Christine Winter Christoph Lemke Reinhard Sohr Wassilios Meissner Daniel Harnack Georg Juckel Rudolf Morgenstern Andreas Kupsch
Received: 26 June 2007 / Accepted: 8 October 2007 / Published online: 26 October 2007 Springer-Verlag 2007
Abstract Despite the beneWt high frequency stimulation (HFS) of the subthalamic nucleus (STN) has on motor symptoms of Parkinsons Disease (PD), accumulating data also suggest eVects of STN-HFS on non-motor behavior. This may be related to the involvement of the STN in the limbic basal ganglia-thalamocortical loops. In the present study we investigated the eVect of acute STN-HFS on neurotransmission in associated structures of these pathways,i.e. the nucleus accumbens (NAc) core and shell as well as the ventral tegmental area (VTA) using in vivo microdialysis. Experiments were performed in anaesthetized nave rats
and rats selectively lesioned in the substantia nigra pars compacta (SNc) or VTA. We demonstrate that: 1. STNHFS leads to an increase in DA in the NAc, 2., these eVects are more pronounced in the NAc shell than in the NAc core, 3. STN-HFS leads to a decrease in GABA in the VTA, 4. preceding lesion of the SNc does not seem to aVect the eVect of STN-HFS on accumbal DA transmission whereas 5. preceding lesion of the VTA seems to prohibit further detection of DA in the NAc. We conclude that STNHFS signiWcantly aVects neurotransmission in the limbic system, which might contribute to explain the non-motor eVects of STN-HFS.
Keywords Subthalamic nucleus
High Frequency Stimulation Nucleus accumbens Dopamine Ventral tegmental area Parkinsons Disease
Introduction
High frequency stimulation (HFS) of the subthalamic nucleus (STN) improves motor symptoms in Parkinsons Disease (PD) (Deuschl et al. 2006; Kumar et al. 1998; Limousin et al. 1998). However, HFS of the STN or closely adjacent structures also aVects psychiatric functions: altered mood and depressive symptoms (Bejjani et al. 2002; Czernecki et al. 2005; Doshi et al. 2002; Funkiewiez et al. 2004, 2006; Okun et al. 2003; Thobois et al. 2002; Witt et al. 2006) with suicide (Albanese et al. 2005), transient manic episodes partly with psychotic symptoms (Herzog et al. 2003; Mandat et al. 2006), mirthful laughter, hilarity (Krack...