Neuroendocrine and behavioral effects of repetitive transcranial magnetic stimulation in a psychopathological animal model are suggestive of antidepressant-like effects

Max Planck Institute of Psychiatry, Munich, Germany.
Neuropsychopharmacology (Impact Factor: 7.05). 05/2001; 24(4):337-49. DOI: 10.1016/S0893-133X(00)00191-3
Source: PubMed


The neuroendocrine and behavioral effects of repetitive transcranial magnetic stimulation (rTMS) were investigated in two rat lines selectively bred for high and low anxiety-related behavior. The stimulation parameters were adjusted according to the results of accurate computer-assisted and magnetic resonance imaging-based reconstructions of the current density distributions induced by rTMS in the rat and human brain, ensuring comparable stimulation patterns in both cases. Adult male rats were treated in two 3-day series under halothane anesthesia. In the forced swim test, rTMS-treatment induced a more active coping strategy in the high anxiety-related behavior rats only (time spent struggling; 332% vs. controls), allowing these animals to reach the performance of low anxiety-related behavior rats. In contrast, rTMS-treated low anxiety-related behavior rats did not change their swimming behavior. The development of active coping strategies in high anxiety-related behavior rats was accompanied by a significantly attenuated stress-induced elevation of plasma corticotropin and corticosterone concentrations. In summary, the behavioral and neuroendocrine effects of rTMS of frontal brain regions in high anxiety-related behavior rats are comparable to the effects of antidepressant drug treatment. Interestingly, in the psychopathological animal model repetitive transcranial magnetic stimulation induced changes in stress coping abilities in the high-anxiety line only.

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    • "We found that during the first 15 minutes into the plethysmograph HAB rats spent relatively less time at high-frequency sniffing mode than LABs. Previous studies have demonstrated that HAB and LAB rats differ in their coping strategies, with HABs displaying reduced exploratory drive and preferring more passive strategies [14], [22]. Our hypothesis is that the reduction in exploratory sniffing that we observed in HAB rats might thus be a function of a decreased motivational state in these animals and interpreted as a sign of preference for passivity, a behavior that is commonly taken as an indicator of increased anxiety [14]. "
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    • "Differences in the trait anxiety level may be accompanied by different coping strategy or resilience to stress. Indeed, rats bred for extremes in anxiety were shown to use active (less anxious) or passive (more anxious) coping strategy in the forced swim [14] [15] and hole-board test [20]. Previously, we have developed two mouse strains having either high-or low-anxiety related behavior (AX and nAX, respectively) as was shown in the EPM, open-field, and light/dark test [28] [31]. "
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    • "In one study, rapid tryptophan depletion did not lead to reemergence of depressive symptoms in adults who had responded to a course of rTMS (O'Reardon et al., 2007), suggesting that the therapeutic effects of rTMS do not depend critically upon central serotonergic tone. Effects on neuroendocrine measures also have been reported in animals (Keck et al., 2001; Hedges et al., 2003; Kito et al., 2010) and in humans undergoing rTMS (Pridmore, 1999; Cohrs et al., 2001; Zwanzger et al., 2003), and hippocampal neurogenesis has been reported in animals (Czeh et al., 2002). A cautionary note about interpreting these animal studies has been sounded by Lisanby and Belmaker (2000): while therapeutic rTMS in humans tends to involve stimulation of a spatially-limited portion of brain tissue, most if not all of the animal brain is exposed to high levels of the magnetic field in these experimental paradigms, due to the different size of animals and the physics of generating magnetic fields. "
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