Decoding of dopaminergic mesolimbic activity and depressive behavior

Leslie Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan 52900, Israel.
Journal of Molecular Neuroscience (Impact Factor: 2.34). 02/2007; 32(1):72-9. DOI: 10.1007/s12031-007-0016-5
Source: PubMed


Dopaminergic mesolimbic and mesocortical systems are involved in hedonia and motivation, two core symptoms of depression. However, their role in the pathophysiology of depression and their manipulation to treat depression has received little attention. Previously, we showed decreased limbic dopamine (DA) neurotransmission in an animal model of depression, Flinder sensitive line (FSL) rats. Here we describe a high correlation between phase-space algorithm of bursting-like activity of DA cells in the ventral tegmental area (VTA) and efficiency of DA release in the accumbens. This bursting-like activity of VTA DA cells of FSL rats is characterized by a low dimension complexity. Treatment with the antidepressant desipramine affected both the dimension complexity of cell firing in the VTA and rate of DA release in the accumbens, as well as alleviating depressive-like behavior. Our findings indicate the potential usefulness of monitoring limbic dopaminergic dynamics in combination with non-linear analysis. Decoding the functionality of the dopaminergic system may help in development of future antidepressant drugs.

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Available from: Alexander Friedman, May 14, 2014
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    • "These analyses characterize the interspike interval (ISI) series by the summation of probability distributions for different durations of ISIs (i.e., firing rate, its range, or standard deviation) or several frequencies (power spectrum). However, the irregularity in the neuronal firing activity is not linear [44] [45] [46] [47] [48] [49] [50] [51] "
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    ABSTRACT: During this last decade, nonlinear analyses have been used to characterize the irregularity that exists in the neuronal data stream of the basal ganglia. In comparison to linear parameters for disparity (i.e., rate, standard deviation, and oscillatory activities), nonlinear analyses focus on complex patterns that are composed of groups of interspike intervals with matching lengths but not necessarily contiguous in the data stream. In light of recent animal and clinical studies, we present a review and commentary on the basal ganglia neuronal entropy in the context of movement disorders.
    05/2013; 2013:742671. DOI:10.1155/2013/742671
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    • "VTA signaling is a known contributing factor to the pathophysiology of a number of psychiatric conditions including depression (Yadid and Friedman, 2008). Previously, we found that treatment with various clinically-employed antidepressants normalized depressive symptoms of FSL rats, an animal model of depression, (Dremencov et al., 2004; 2005; 2006; Yadid et al., 2000; Zangen et al., 2001) in parallel to stabilization of VTA functionality (Friedman et al., 2005; 2007; 2008; 2009; Yadid and Friedman, 2008). "
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    ABSTRACT: Depressive disorders affect approximately 5% of the population in any given year. Deep brain stimulation (DBS) was previously shown to have a long-lasting normalizing effect on the ventral tegmental area (VTA) firing pattern in Flinders-Sensitive-Line (FSL) rats, an animal model for depression. In the current study, we aimed to find a possible electrophysiological mechanism that underlies this adaptation. Local-field-potential (LFP) time-series were recorded in the VTA of conscious, freely-moving FSL (depressive-like) and control Sprague-Dawley (SD) rats. We found that 42% of recordings both from FSL and SD rats showed clear peaks between 1-8Hz. Within these recordings, SD rats mostly demonstrated a single, uniform peak at frequencies of 1-3Hz. However, FSL rats demonstrated a significantly higher amount of recordings with double or triple peaks, at frequencies of 1-8Hz. In addition to the power spectrum, autocorrelation calculation of LFP recordings also showed significant differences between groups. We examined acute DBS of the VTA as a novel method for ameliorating these electrophysiological aberrations, in addition to attenuation of depressive-like behavior. The pattern of stimulation was fashioned to mimic the firing pattern of VTA neurons in control rats, as shown in previous work. The results suggest that treatment with programmed acute electrical stimulation of the VTA substantially restores VTA LFP in FSL rats to normal activity levels, parallel to alleviation of depressive-like behavior, for an extended period of time.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 05/2011; 22(1):64-71. DOI:10.1016/j.euroneuro.2011.04.005 · 4.37 Impact Factor
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    • "Of the parameters monitored, two, the head to body turn angle and the heading of the rat, changed significantly within 1 to 3 days upon administration of paroxetine or desipramine. Correlation dimension is a nonlinear measurement that characterizes the complexity degree of dynamic systems (Friedman et al. 2007). When the interest of the rats in their environment is constant, their behavior is monotonic. "
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    ABSTRACT: Although depressive disorders affect approximately 5% of the population in developed countries each year, current antidepressants usually require several weeks to produce beneficial clinical effects and are only effective in about 55% of patients. Therefore, early prediction of the effectiveness of a particular antidepressant for a patient is important for effective pharmacological treatment of depression. In this study, we examined a new method, based on mathematical analyses, of exploratory behavior for predicting the effectiveness of particular antidepressants shortly after initiation of treatment. By using this method, we were able to predict the effectiveness of antidepressants 1-3 days after initiation of treatment in individual subjects.
    Journal of Molecular Neuroscience 03/2009; 39(1-2):256-61. DOI:10.1007/s12031-009-9176-9 · 2.34 Impact Factor
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