Characterizing Effects of Subthalamic Nucleus Deep Brain Stimulation on Methamphetamine-Induced Circling Behavior in Hemi-Parkinsonian Rats

The unilateral 6-hydroxydopamine (6-OHDA) lesioned rat model is frequently used to study the effects of subthalamic nucleus (STN) deep brain stimulation (DBS) for the treatment of Parkinson's disease. However, systematic knowledge of the effects of DBS parameters on behavior in this animal model is lacking. The goal of this study was to characterize the effects of DBS on methamphetamine-induced circling in the unilateral 6-OHDA lesioned rat. DBS parameters tested include stimulation amplitude, stimulation frequency, methamphetamine dose, stimulation polarity, and anatomical location of the electrode. When an appropriate stimulation amplitude and dose of methamphetamine were applied, high-frequency stimulation (>; 130 Hz), but not low frequency stimulation (<; 10 Hz), reversed the bias in ipsilateral circling without inhibiting movement. This characteristic frequency tuning profile was only generated when at least one electrode used during bipolar stimulation was located within the STN. No difference was found between bipolar stimulation and monopolar stimulation when the most effective electrode contact was selected, indicating that monopolar stimulation could be used in future experiments. Methamphetamine-induced circling is a simple, reliable, and sensitive behavioral test and holds potential for high-throughput study of the effects of STN DBS in unilaterally lesioned rats.

[1]  Jean-Michel Deniau,et al.  High Frequency Stimulation of the Subthalamic Nucleus , 2005 .

[2]  Y. Agid,et al.  Dopaminergic sprouting in the rat striatum after partial lesion of the substantia nigra , 1996, Brain Research.

[3]  U. Ungerstedt,et al.  Quantitative recording of rotational behavior in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine system. , 1970, Brain research.

[4]  Jan Gimsa,et al.  Optimizing a Rodent Model of Parkinson's Disease for Exploring the Effects and Mechanisms of Deep Brain Stimulation , 2011, Parkinson's disease.

[5]  Warren M. Grill,et al.  Relative contributions of local cell and passing fiber activation and silencing to changes in thalamic fidelity during deep brain stimulation and lesioning: a computational modeling study , 2011, Journal of Computational Neuroscience.

[6]  Y. Agid,et al.  Long‐term results of a multicenter study on subthalamic and pallidal stimulation in Parkinson's disease , 2010, Movement disorders : official journal of the Movement Disorder Society.

[7]  E. Bézard,et al.  Electrophysiological and metabolic evidence that high‐frequency stimulation of the subthalamic nucleus bridles neuronal activity in the subthalamic nucleus and the substantia nigra reticulata , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  S. Ara,et al.  White fiber dissection of brain; the internal capsule: a cadaveric study. , 2010, Turkish neurosurgery.

[9]  C. Sortwell,et al.  A functionally relevant and long‐term model of deep brain stimulation of the rat subthalamic nucleus: advantages and considerations , 2010, The European journal of neuroscience.

[10]  K. Sugiyama,et al.  Improvements in motor behavioral tests during deep brain stimulation of the subthalamic nucleus in rats with different degrees of unilateral parkinsonism , 2006, Brain Research.

[11]  Murtaza Z Mogri,et al.  Optical Deconstruction of Parkinsonian Neural Circuitry , 2009, Science.

[12]  Christos Tsironis,et al.  Levodopa-induced dyskinesia and rotational behavior in hemiparkinsonian rats: Independent features or components of the same phenomenon? , 2006, Behavioural Brain Research.

[13]  Y. Temel,et al.  High frequency stimulation of the subthalamic nucleus improves speed of locomotion but impairs forelimb movement in Parkinsonian rats , 2007, Neuroscience.

[14]  Peter Brown,et al.  Effects of low-frequency stimulation of the subthalamic nucleus on movement in Parkinson's disease , 2007, Experimental Neurology.

[15]  A. Benabid,et al.  The impact on Parkinson’s disease of electrical parameter settings in STN stimulation , 2002, Neurology.

[16]  Elena Moro,et al.  Subthalamic nucleus stimulation: improvements in outcome with reprogramming. , 2006, Archives of neurology.

[17]  C. Bjarkam,et al.  Chronic subthalamic high‐frequency deep brain stimulation in Parkinson's disease – a histopathological study , 2007, European journal of neurology.

[18]  J. Dostrovsky,et al.  High-frequency Synchronization of Neuronal Activity in the Subthalamic Nucleus of Parkinsonian Patients with Limb Tremor , 2000, The Journal of Neuroscience.

[19]  C. McIntyre,et al.  Current steering to control the volume of tissue activated during deep brain stimulation , 2008, Brain Stimulation.

[20]  A. Morel,et al.  Single-unit analysis of the pallidum, thalamus and subthalamic nucleus in parkinsonian patients , 2000, Neuroscience.

[21]  N. Kumar,et al.  Bilateral Deep Brain Stimulation vs Best Medical Therapy for Patients With Advanced Parkinson Disease: A Randomized Controlled Trial , 2009 .

[22]  J. Kleinman,et al.  Spontaneous asymmetric circling behavior in hemi-parkinsonism; a human equivalent of the lesioned-circling rodent behavior. , 1987, Life sciences.

[23]  Joachim Gross,et al.  Ten‐Hertz stimulation of subthalamic nucleus deteriorates motor symptoms in Parkinson's disease , 2004, Movement disorders : official journal of the Movement Disorder Society.

[24]  P. Lang,et al.  Panic and fear induced by deep brain stimulation , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[25]  Michael S Okun,et al.  Deep brain stimulation in the internal capsule and nucleus accumbens region: responses observed during active and sham programming , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[26]  F. Luo,et al.  High frequency stimulation of the subthalamic nucleus improves treadmill locomotion in unilateral 6-hydroxydopamine lesioned rats , 2003, Brain Research.

[27]  Warren M Grill,et al.  Computational modeling of epidural cortical stimulation , 2008, Journal of neural engineering.

[28]  M. Horne,et al.  Comparison of the basal ganglia in rats, marmosets, macaques, baboons, and humans: Volume and neuronal number for the output, internal relay, and striatal modulating nuclei , 2002, The Journal of comparative neurology.

[29]  Warren M. Grill,et al.  Selection of stimulus parameters for deep brain stimulation , 2004, Clinical Neurophysiology.

[30]  M. Amalric,et al.  High frequency stimulation of the subthalamic nucleus has beneficial antiparkinsonian effects on motor functions in rats, but less efficiency in a choice reaction time task , 2003, The European journal of neuroscience.

[31]  P. Brown,et al.  Frequency dependent effects of subthalamic nucleus stimulation in Parkinson's disease , 2005, Neuroscience Letters.

[32]  Rudolf Morgenstern,et al.  Deep brain stimulation of subthalamic neurons increases striatal dopamine metabolism and induces contralateral circling in freely moving 6-hydroxydopamine-lesioned rats , 2002, Neuroscience Letters.

[33]  S D Glick,et al.  Turning in circles: the neuropharmacology of rotation. , 1976, Life sciences.

[34]  F. Luo,et al.  High-frequency stimulation of the subthalamic nucleus reverses limb-use asymmetry in rats with unilateral 6-hydroxydopamine lesions , 2004, Brain Research.

[35]  W. Grill,et al.  Mechanisms of deep brain stimulation in movement disorders as revealed by changes in stimulus frequency , 2011, Neurotherapeutics.