BACKGROUND: Subcallosal cingulate gyrus (SCG) deep brain stimulation (DBS) is being investigated as a treatment for major depression. We report on the effects of ventromedial prefrontal cortex (vmPFC) DBS in rats, focusing on possible mechanisms involved in an antidepressant-like response in the forced swim test (FST). METHODS: The outcome of vmPFC stimulation alone or combined with different types of lesions, including serotonin (5-HT) or norepineprhine (NE) depletion, was characterized in the FST. We also explored the effects of DBS on novelty-suppressed feeding, learned helplessness, and sucrose consumption in animals predisposed to helplessness. RESULTS: Stimulation at parameters approximating those used in clinical practice induced a significant antidepressant-like response in the FST. Ventromedial PFC lesions or local muscimol injections did not lead to a similar outcome. However, animals treated with vmPFC ibotenic acid lesions still responded to DBS, suggesting that the modulation of fiber near the electrodes could play a role in the antidepressant-like effects of stimulation. Also important was the integrity of the serotonergic system, as the effects of DBS in the FST were completely abolished in animals bearing 5-HT, but not NE, depleting lesions. In addition, vmPFC stimulation induced a sustained increase in hippocampal 5-HT levels. Preliminary work with other models showed that DBS was also able to influence specific aspects of depressive-like states in rodents, including anxiety and anhedonia, but not helplessness. CONCLUSIONS: Our study suggests that vmPFC DBS in rats may be useful to investigate mechanisms involved in the antidepressant effects of SCG DBS.
BACKGROUND: Subcallosal cingulate gyrus (SCG) deep brain stimulation (DBS) is being investigated as a treatment for major depression. We report on the effects of ventromedial prefrontal cortex (vmPFC) DBS in rats, focusing on possible mechanisms involved in an antidepressant-like response in the forced swim test (FST). METHODS: The outcome of vmPFC stimulation alone or combined with different types of lesions, including serotonin (5-HT) or norepineprhine (NE) depletion, was characterized in the FST. We also explored the effects of DBS on novelty-suppressed feeding, learned helplessness, and sucrose consumption in animals predisposed to helplessness. RESULTS: Stimulation at parameters approximating those used in clinical practice induced a significant antidepressant-like response in the FST. Ventromedial PFC lesions or local muscimol injections did not lead to a similar outcome. However, animals treated with vmPFC ibotenic acid lesions still responded to DBS, suggesting that the modulation of fiber near the electrodes could play a role in the antidepressant-like effects of stimulation. Also important was the integrity of the serotonergic system, as the effects of DBS in the FST were completely abolished in animals bearing 5-HT, but not NE, depleting lesions. In addition, vmPFC stimulation induced a sustained increase in hippocampal 5-HT levels. Preliminary work with other models showed that DBS was also able to influence specific aspects of depressive-like states in rodents, including anxiety and anhedonia, but not helplessness. CONCLUSIONS: Our study suggests that vmPFC DBS in rats may be useful to investigate mechanisms involved in the antidepressant effects of SCG DBS.
Authors: K-W Lee; L Westin; J Kim; J C Chang; Y-S Oh; B Amreen; J Gresack; M Flajolet; D Kim; A Aperia; Y Kim; P Greengard Journal: Mol Psychiatry Date: 2015-09-15 Impact factor: 15.992
Authors: David Carlson; Lisa K David; Neil M Gallagher; Mai-Anh T Vu; Matthew Shirley; Rainbo Hultman; Joyce Wang; Caley Burrus; Colleen A McClung; Sunil Kumar; Lawrence Carin; Stephen D Mague; Kafui Dzirasa Journal: Biol Psychiatry Date: 2017-06-15 Impact factor: 13.382
Authors: Roman Reznikov; Francis Rodriguez Bambico; Mustansir Diwan; Roger J Raymond; Mina G Nashed; José N Nobrega; Clement Hamani Journal: Neuropsychopharmacology Date: 2017-09-01 Impact factor: 7.853
Authors: Sunil Kumar; Sherilynn J Black; Rainbo Hultman; Steven T Szabo; Kristine D DeMaio; Jeanette Du; Brittany M Katz; Guoping Feng; Herbert E Covington; Kafui Dzirasa Journal: J Neurosci Date: 2013-01-16 Impact factor: 6.167