Deep Brain Stimulation of Hemiparkinsonian Rats with Unipolar and Bipolar Electrodes for up to 6 Weeks: Behavioral Testing of Freely Moving Animals

Although the clinical use of deep brain stimulation (DBS) is increasing, its basic mechanisms of action are still poorly understood. Platinum/iridium electrodes were inserted into the subthalamic nucleus of rats with unilateral 6-OHDA-induced lesions of the medial forebrain bundle. Six behavioral parameters were compared with respect to their potential to detect DBS effects. Locomotor function was quantified by (i) apomorphine-induced rotation, (ii) initiation time, (iii) the number of adjusting steps in the stepping test, and (iv) the total migration distance in the open field test. Sensorimotor neglect and anxiety were quantified by (v) the retrieval bias in the corridor test and (vi) the ratio of migration distance in the center versus in the periphery in the open field test, respectively. In our setup, unipolar stimulation was found to be more efficient than bipolar stimulation for achieving beneficial long-term DBS effects. Performance in the apomorphine-induced rotation test showed no improvement after 6 weeks. DBS reduced the initiation time of the contralateral paw in the stepping test after 3 weeks of DBS followed by 3 weeks without DBS. Similarly, sensorimotor neglect was improved. The latter two parameters were found to be most appropriate for judging therapeutic DBS effects.

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Correlation between Two Parameters of Mice Behaviour in the Open Field Test

Acta Facultatis Medicae Naissensis ◽

10.1515/afmnai-2017-0032 ◽

2017 ◽

Vol 34 (4) ◽

pp. 321-327

Author(s):

Nikola M. Stojanović ◽

Pavle J. Randjelović ◽

Niko S. Radulović

Keyword(s):

Drug Discovery ◽

Motor Activity ◽

Open Field ◽

Field Test ◽

Direct Observation ◽

Open Field Test ◽

Video Recording ◽

Animal Behaviour ◽

Two Parameters

Summary The open field test is being used extensively for the determination of different aspects of animal behaviour for over seventy years. The correlation between different behavioural parameters obtained in this test, although previously studied, is still debatable. Thus, we aimed to analyze and correlate behaviour scores to estimate the importance of individual parameters in this type of experiment. The open field test was performed on male BALB/c mice treated with either saline (10 ml/kg) or diazepam (2 mg/kg), one hour before the experiment. The behaviour scores (number of squares crossed and rearings performed) obtained either by video recording or direct observation, during a five-minute experiment, were compared using a t-test and were tested for correlation. As expected, diazepam caused an increase in the number of squares crossed and rearings performed by the animals. The number of rearings was statistically different between the groups monitored in two different ways. The correlations between the behaviour scores obtained in the two modes of monitoring for all groups were moderate/strong positive ones. The correlation analyses revealed that the amount of information conveyed by a single behaviour parameter, either the number of squares crossed or the number of rearings, could be sufficient to estimate the animals’ motor activity in the open field test. Also, the results of this test could provide clues to very important piece of information in drug discovery, i.e. the general animal behaviour under the influence of CNS acting drugs in an experiment.

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Mood Regulatory Actions of Active and Sham Nucleus Accumbens Deep Brain Stimulation in Antidepressant Resistant Rats

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.644921 ◽

2021 ◽

Vol 15 ◽

Author(s):

Rajas P. Kale ◽

Thanh Thanh L. Nguyen ◽

J. Blair Price ◽

Nathanael J. Yates ◽

Ken Walder ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Nucleus Accumbens ◽

Open Field ◽

Brain Stimulation ◽

Forced Swim Test ◽

Electrode Placement ◽

Daily Injection ◽

Forced Swim ◽

Immobility Time ◽

Deep Brain

The antidepressant actions of deep brain stimulation (DBS) are associated with progressive neuroadaptations within the mood network, modulated in part, by neurotrophic mechanisms. We investigated the antidepressant-like effects of chronic nucleus accumbens (NAc) DBS and its association with change in glycogen synthase kinase 3 (GSK3) and mammalian target of rapamycin (mTOR) expression in the infralimbic cortex (IL), and the dorsal (dHIP) and ventral (vHIP) subregions of the hippocampus of antidepressant resistant rats. Antidepressant resistance was induced via daily injection of adrenocorticotropic hormone (ACTH; 100 μg/day; 15 days) and confirmed by non-response to tricyclic antidepressant treatment (imipramine, 10 mg/kg). Portable microdevices provided continuous bilateral NAc DBS (130 Hz, 200 μA, 90 μs) for 7 days. A control sham electrode group was included, together with ACTH- and saline-treated control groups. Home cage monitoring, open field, sucrose preference, and, forced swim behavioral tests were performed. Post-mortem levels of GSK3 and mTOR, total and phosphorylated, were determined with Western blot. As previously reported, ACTH treatment blocked the immobility-reducing effects of imipramine in the forced swim test. In contrast, treatment with either active DBS or sham electrode placement in the NAc significantly reduced forced swim immobility time in ACTH-treated animals. This was associated with increased homecage activity in the DBS and sham groups relative to ACTH and saline groups, however, no differences in locomotor activity were observed in the open field test, nor were any group differences seen for sucrose consumption across groups. The antidepressant-like actions of NAc DBS and sham electrode placements were associated with an increase in levels of IL and vHIP phospho-GSK3β and phospho-mTOR, however, no differences in these protein levels were observed in the dHIP region. These data suggest that early response to electrode placement in the NAc, irrespective of whether active DBS or sham, has antidepressant-like effects in the ACTH-model of antidepressant resistance associated with distal upregulation of phospho-GSK3β and phospho-mTOR in the IL and vHIP regions of the mood network.

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Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Unipolar and Bipolar Depression

Yearbook of Neurology and Neurosurgery ◽

10.1016/j.yneu.2012.05.058 ◽

2012 ◽

Vol 2012 ◽

pp. 241-243

Author(s):

P. House

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Bipolar Depression ◽

Treatment Resistant ◽

Deep Brain

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Deep Brain Stimulation Aids Resistant Depression

Internal Medicine News ◽

10.1016/s1097-8690(08)71087-4 ◽

2008 ◽

Vol 41 (19) ◽

pp. 20

Author(s):

MICHELE G. SULLIVAN

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Resistant Depression ◽

Deep Brain

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Nicht-medikamentöse Optionen zur Behandlung pharmakoresistenter Epilepsien

Therapeutische Umschau ◽

10.1024/0040-5930/a001023 ◽

2018 ◽

Vol 75 (7) ◽

pp. 448-454

Author(s):

Thomas Grunwald ◽

Judith Kröll

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Tiefe Hirnstimulation ◽

Ketogene Diät ◽

Deep Brain

Zusammenfassung. Wenn mit den ersten beiden anfallspräventiven Medikamenten keine Anfallsfreiheit erzielt werden konnte, so ist die Wahrscheinlichkeit, dies mit anderen Medikamenten zu erreichen, nur noch ca. 10 %. Es sollte dann geprüft werden, warum eine Pharmakoresistenz besteht und ob ein epilepsiechirurgischer Eingriff zur Anfallsfreiheit führen kann. Ist eine solche Operation nicht möglich, so können palliative Verfahren wie die Vagus-Nerv-Stimulation (VNS) und die tiefe Hirnstimulation (Deep Brain Stimulation) in eine bessere Anfallskontrolle ermöglichen. Insbesondere bei schweren kindlichen Epilepsien stellt auch die ketogene Diät eine zu erwägende Option dar.

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