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  • 1
    Publication Date: 2003-08-09
    Description: Various chronic antidepressant treatments increase adult hippocampal neurogenesis, but the functional importance of this phenomenon remains unclear. Here, using genetic and radiological methods, we show that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants. Serotonin 1A receptor null mice were insensitive to the neurogenic and behavioral effects of fluoxetine, a serotonin selective reuptake inhibitor. X-irradiation of a restricted region of mouse brain containing the hippocampus prevented the neurogenic and behavioral effects of two classes of antidepressants. These findings suggest that the behavioral effects of chronic antidepressants may be mediated by the stimulation of neurogenesis in the hippocampus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Santarelli, Luca -- Saxe, Michael -- Gross, Cornelius -- Surget, Alexandre -- Battaglia, Fortunato -- Dulawa, Stephanie -- Weisstaub, Noelia -- Lee, James -- Duman, Ronald -- Arancio, Ottavio -- Belzung, Catherine -- Hen, Rene -- New York, N.Y. -- Science. 2003 Aug 8;301(5634):805-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neurobiology and Behavior, Columbia University, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12907793" target="_blank"〉PubMed〈/a〉
    Keywords: 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology ; Animals ; Antidepressive Agents/*pharmacology ; Antidepressive Agents, Second-Generation/pharmacology ; Antidepressive Agents, Tricyclic/pharmacology ; Behavior, Animal/*drug effects ; Cell Division/drug effects/radiation effects ; Conditioning (Psychology) ; Dentate Gyrus/cytology/drug effects/physiology ; Fear ; Feeding Behavior/drug effects ; Fluoxetine/*pharmacology ; Grooming/drug effects ; Hippocampus/cytology/drug effects/*physiology/radiation effects ; Long-Term Potentiation/radiation effects ; Male ; Mice ; Mice, Knockout ; Neurons/drug effects/*physiology ; Receptors, Serotonin/genetics/metabolism ; Receptors, Serotonin, 5-HT1 ; Stress, Physiological/drug therapy/physiopathology ; Synaptic Transmission/radiation effects
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-10-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hen, R -- New York, N.Y. -- Science. 1999 Sep 24;285(5436):2068-9; author reply 2069-70.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10523202" target="_blank"〉PubMed〈/a〉
    Keywords: *Alcohol Drinking ; Animals ; Crosses, Genetic ; *Gene Frequency ; Mice ; Mice, Knockout/*genetics ; Receptor, Serotonin, 5-HT1B ; Receptors, Serotonin/genetics/*physiology ; Stem Cells
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2006-07-29
    Description: Serotonin [5-hydroxytryptamine (5-HT)] neurotransmission in the central nervous system modulates depression and anxiety-related behaviors in humans and rodents, but the responsible downstream receptors remain poorly understood. We demonstrate that global disruption of 5-HT2A receptor (5HT2AR) signaling in mice reduces inhibition in conflict anxiety paradigms without affecting fear-conditioned and depression-related behaviors. Selective restoration of 5HT2AR signaling to the cortex normalized conflict anxiety behaviors. These findings indicate a specific role for cortical 5HT2AR function in the modulation of conflict anxiety, consistent with models of cortical, "top-down" influences on risk assessment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weisstaub, Noelia V -- Zhou, Mingming -- Lira, Alena -- Lambe, Evelyn -- Gonzalez-Maeso, Javier -- Hornung, Jean-Pierre -- Sibille, Etienne -- Underwood, Mark -- Itohara, Shigeyoshi -- Dauer, William T -- Ansorge, Mark S -- Morelli, Emanuela -- Mann, J John -- Toth, Miklos -- Aghajanian, George -- Sealfon, Stuart C -- Hen, Rene -- Gingrich, Jay A -- KO8 MH01711/MH/NIMH NIH HHS/ -- P01 DA12923/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 2006 Jul 28;313(5786):536-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Columbia University and the New York State Psychiatric Institute, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16873667" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anxiety/*physiopathology ; Cerebral Cortex/*metabolism ; Conditioning (Psychology) ; Conflict (Psychology) ; Depression/physiopathology ; Exploratory Behavior ; Fear ; Limbic System/metabolism ; Mice ; Mice, Knockout ; Patch-Clamp Techniques ; Periaqueductal Gray/metabolism ; Prosencephalon/metabolism ; Receptor, Serotonin, 5-HT2A/genetics/*metabolism ; Receptor, Serotonin, 5-HT2C/metabolism ; Receptors, Neurotransmitter/metabolism ; Risk-Taking ; Serotonin/physiology ; *Signal Transduction ; Synaptic Transmission
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-01-20
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2041961/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2041961/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scharfman, Helen E -- Hen, Rene -- R01 NS037562/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2007 Jan 19;315(5810):336-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Pharmacology and Neurology, Columbia University, and Center for Neural Recovery and Rehabilitation Research, Helen Hayes Hospital, West Haverstraw, NY 10993-1195, USA. scharfmanh@helenhayeshosp.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17234934" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antidepressive Agents/pharmacology ; Brain/cytology/*physiology ; Brain Diseases/physiopathology/therapy ; Cell Movement ; Cell Proliferation ; Cell Survival ; Dentate Gyrus/cytology/physiology ; Emotions ; Humans ; Mental Processes ; Neuronal Plasticity ; Neurons/*cytology/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2013-06-08
    Description: Although cortico-striato-thalamo-cortical (CSTC) circuit dysregulation is correlated with obsessive compulsive disorder (OCD), causation cannot be tested in humans. We used optogenetics in mice to simulate CSTC hyperactivation observed in OCD patients. Whereas acute orbitofrontal cortex (OFC)-ventromedial striatum (VMS) stimulation did not produce repetitive behaviors, repeated hyperactivation over multiple days generated a progressive increase in grooming, a mouse behavior related to OCD. Increased grooming persisted for 2 weeks after stimulation cessation. The grooming increase was temporally coupled with a progressive increase in light-evoked firing of postsynaptic VMS cells. Both increased grooming and evoked firing were reversed by chronic fluoxetine, a first-line OCD treatment. Brief but repeated episodes of abnormal circuit activity may thus set the stage for the development of persistent psychopathology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954809/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954809/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ahmari, Susanne E -- Spellman, Timothy -- Douglass, Neria L -- Kheirbek, Mazen A -- Simpson, H Blair -- Deisseroth, Karl -- Gordon, Joshua A -- Hen, Rene -- K01 MH099371/MH/NIMH NIH HHS/ -- K01MH099371/MH/NIMH NIH HHS/ -- K08 MH087718/MH/NIMH NIH HHS/ -- K08MH087718/MH/NIMH NIH HHS/ -- K24 MH091555/MH/NIMH NIH HHS/ -- R01 MH096274/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Jun 7;340(6137):1234-9. doi: 10.1126/science.1234733.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. sea2103@columbia.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23744948" target="_blank"〉PubMed〈/a〉
    Keywords: Adenoviridae ; Animals ; Artificial Gene Fusion ; Bacterial Proteins/genetics ; Behavior, Animal ; Corpus Striatum/drug effects/*physiopathology ; Electric Stimulation ; Fluoxetine/pharmacology ; Frontal Lobe/drug effects/*physiopathology ; Luminescent Proteins/genetics ; Male ; Mice ; Obsessive-Compulsive Disorder/*physiopathology/*psychology ; Optogenetics ; Rhodopsin/biosynthesis/genetics ; Serotonin Uptake Inhibitors/pharmacology ; Thalamus/drug effects/*physiopathology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2004-10-30
    Description: Reduced serotonin transporter (5-HTT) expression is associated with abnormal affective and anxiety-like symptoms in humans and rodents, but the mechanism of this effect is unknown. Transient inhibition of 5-HTT during early development with fluoxetine, a commonly used serotonin selective reuptake inhibitor, produced abnormal emotional behaviors in adult mice. This effect mimicked the behavioral phenotype of mice genetically deficient in 5-HTT expression. These findings indicate a critical role of serotonin in the maturation of brain systems that modulate emotional function in the adult and suggest a developmental mechanism to explain how low-expressing 5-HTT promoter alleles increase vulnerability to psychiatric disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ansorge, Mark S -- Zhou, Mingming -- Lira, Alena -- Hen, Rene -- Gingrich, Jay A -- New York, N.Y. -- Science. 2004 Oct 29;306(5697):879-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sackler Institute for Developmental Psychobiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15514160" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Newborn ; *Anxiety/chemically induced ; Avoidance Learning/drug effects ; Behavior, Animal/drug effects ; Brain/drug effects/growth & development ; Central Nervous System/drug effects/growth & development ; *Emotions/drug effects ; Feeding Behavior/drug effects ; Fluoxetine/adverse effects/*toxicity ; Humans ; Membrane Glycoproteins/antagonists & inhibitors/genetics/*physiology ; Membrane Transport Modulators ; Membrane Transport Proteins/antagonists & inhibitors/genetics/*physiology ; Mice ; Motor Activity/drug effects ; Nerve Tissue Proteins/antagonists & inhibitors/genetics/*physiology ; Polymorphism, Genetic ; Random Allocation ; Serotonin Plasma Membrane Transport Proteins ; Serotonin Uptake Inhibitors/adverse effects/*toxicity ; Stress, Physiological
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2011-04-05
    Description: Adult hippocampal neurogenesis is a unique form of neural circuit plasticity that results in the generation of new neurons in the dentate gyrus throughout life. Neurons that arise in adults (adult-born neurons) show heightened synaptic plasticity during their maturation and can account for up to ten per cent of the entire granule cell population. Moreover, levels of adult hippocampal neurogenesis are increased by interventions that are associated with beneficial effects on cognition and mood, such as learning, environmental enrichment, exercise and chronic treatment with antidepressants. Together, these properties of adult neurogenesis indicate that this process could be harnessed to improve hippocampal functions. However, despite a substantial number of studies demonstrating that adult-born neurons are necessary for mediating specific cognitive functions, as well as some of the behavioural effects of antidepressants, it is unknown whether an increase in adult hippocampal neurogenesis is sufficient to improve cognition and mood. Here we show that inducible genetic expansion of the population of adult-born neurons through enhancing their survival improves performance in a specific cognitive task in which two similar contexts need to be distinguished. Mice with increased adult hippocampal neurogenesis show normal object recognition, spatial learning, contextual fear conditioning and extinction learning but are more efficient in differentiating between overlapping contextual representations, which is indicative of enhanced pattern separation. Furthermore, stimulation of adult hippocampal neurogenesis, when combined with an intervention such as voluntary exercise, produces a robust increase in exploratory behaviour. However, increasing adult hippocampal neurogenesis alone does not produce a behavioural response like that induced by anxiolytic agents or antidepressants. Together, our findings suggest that strategies that are designed to increase adult hippocampal neurogenesis specifically, by targeting the cell death of adult-born neurons or by other mechanisms, may have therapeutic potential for reversing impairments in pattern separation and dentate gyrus dysfunction such as those seen during normal ageing.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084370/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084370/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sahay, Amar -- Scobie, Kimberly N -- Hill, Alexis S -- O'Carroll, Colin M -- Kheirbek, Mazen A -- Burghardt, Nesha S -- Fenton, Andre A -- Dranovsky, Alex -- Hen, Rene -- 1K99MH86615-01/MH/NIMH NIH HHS/ -- K08 MH079088/MH/NIMH NIH HHS/ -- K08 MH079088-01/MH/NIMH NIH HHS/ -- K08 MH079088-02/MH/NIMH NIH HHS/ -- K08 MH079088-03/MH/NIMH NIH HHS/ -- K08 MH079088-03S1/MH/NIMH NIH HHS/ -- K08 MH079088-04/MH/NIMH NIH HHS/ -- K08 MH079088-05/MH/NIMH NIH HHS/ -- K99 MH086615/MH/NIMH NIH HHS/ -- K99 MH086615-02/MH/NIMH NIH HHS/ -- R01 MH068542/MH/NIMH NIH HHS/ -- R01 MH091844/MH/NIMH NIH HHS/ -- R01 MH091844-01/MH/NIMH NIH HHS/ -- R01 MH091844-02/MH/NIMH NIH HHS/ -- R01 MH091844-03/MH/NIMH NIH HHS/ -- T32 HD007430/HD/NICHD NIH HHS/ -- England -- Nature. 2011 Apr 28;472(7344):466-70. doi: 10.1038/nature09817. Epub 2011 Apr 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Columbia University, New York, New York 10032, USA. as2619@columbia.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21460835" target="_blank"〉PubMed〈/a〉
    Keywords: Affect/*physiology ; Aging/drug effects/pathology/*physiology ; Animals ; Antidepressive Agents/pharmacology ; Anxiety/physiopathology/therapy ; Apoptosis/drug effects ; Cell Survival/drug effects ; Cognition/drug effects/*physiology ; Conditioning, Classical/drug effects/physiology ; Dentate Gyrus/cytology/pathology/physiology/physiopathology ; Exploratory Behavior/drug effects/physiology ; Extinction, Psychological/drug effects/physiology ; Fear/physiology/psychology ; Female ; Hippocampus/*cytology/pathology/*physiology/physiopathology ; Learning/drug effects/physiology ; Long-Term Potentiation/drug effects/physiology ; Male ; Memory/drug effects/physiology ; Mice ; Mice, Knockout ; Mice, Transgenic ; *Models, Neurological ; Neural Stem Cells/cytology/drug effects/metabolism ; Neurogenesis/drug effects/*physiology ; Neuronal Plasticity/drug effects/physiology ; Physical Conditioning, Animal/physiology ; Synapses/drug effects/metabolism ; bcl-2-Associated X Protein/deficiency/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2014-11-11
    Description: Innate behaviours are observed in naive animals without prior learning or experience, suggesting that the neural circuits that mediate these behaviours are genetically determined and stereotyped. The neural circuits that convey olfactory information from the sense organ to the cortical and subcortical olfactory centres have been anatomically defined, but the specific pathways responsible for innate responses to volatile odours have not been identified. Here we devise genetic strategies that demonstrate that a stereotyped neural circuit that transmits information from the olfactory bulb to cortical amygdala is necessary for innate aversive and appetitive behaviours. Moreover, we use the promoter of the activity-dependent gene arc to express the photosensitive ion channel, channelrhodopsin, in neurons of the cortical amygdala activated by odours that elicit innate behaviours. Optical activation of these neurons leads to appropriate behaviours that recapitulate the responses to innate odours. These data indicate that the cortical amygdala plays a critical role in generating innate odour-driven behaviours but do not preclude its participation in learned olfactory behaviours.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231015/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231015/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Root, Cory M -- Denny, Christine A -- Hen, Rene -- Axel, Richard -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Nov 13;515(7526):269-73. doi: 10.1038/nature13897. Epub 2014 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience and the Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. ; 1] Department of Biological Sciences, New York State Psychiatric Institute, New York, New York 10032, USA [2] Department of Neuroscience and Psychiatry, New York State Psychiatric Institute, New York, New York 10032, USA [3] Division of Integrative Neuroscience, New York State Psychiatric Institute, New York, New York 10032, USA. ; 1] Department of Neuroscience and Psychiatry, New York State Psychiatric Institute, New York, New York 10032, USA [2] Division of Integrative Neuroscience, New York State Psychiatric Institute, New York, New York 10032, USA [3] Department of Pharmacology, Columbia University, New York State Psychiatric Institute, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25383519" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/cytology/*physiology ; Animals ; Behavior/*physiology ; Learning/physiology ; Mice ; Neurons/physiology ; Odors/*analysis ; Olfactory Bulb/cytology/physiology ; Olfactory Pathways/cytology/physiology ; Olfactory Perception/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 1994-09-23
    Description: The neuromodulator serotonin (5-hydroxytryptamine, 5-HT) has been associated with mood disorders such as depression, anxiety, and impulsive violence. To define the contribution of 5-HT receptor subtypes to behavior, mutant mice lacking the 5-HT1B receptor were generated by homologous recombination. These mice did not exhibit any obvious developmental or behavioral defects. However, the hyperlocomotor effect of the 5-HT1A/1B agonist RU24969 was absent in mutant mice, indicating that this effect is mediated by 5-HT1B receptors. Moreover, when confronted with an intruder, mutant mice attacked the intruder faster and more intensely than did wild-type mice, suggesting the participation of 5-HT1B receptors in aggressive behavior.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saudou, F -- Amara, D A -- Dierich, A -- LeMeur, M -- Ramboz, S -- Segu, L -- Buhot, M C -- Hen, R -- New York, N.Y. -- Science. 1994 Sep 23;265(5180):1875-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire de Genetique Moleculaire des Eucaryotes du CNRS, U184 de l'INSERM, Faculte de Medecine, Strasbourg, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8091214" target="_blank"〉PubMed〈/a〉
    Keywords: Aggression/*physiology ; Animals ; Brain Chemistry ; Chimera ; Female ; Indoles/pharmacology ; Male ; Mice ; Motor Activity/drug effects ; Mutation ; Pindolol/analogs & derivatives/metabolism ; Receptor, Serotonin, 5-HT1B ; Receptors, Serotonin/analysis/genetics/*physiology ; Recombination, Genetic ; Serotonin Receptor Agonists/pharmacology
    Print ISSN: 0036-8075
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  • 10
    Publication Date: 2011-12-24
    Description: Antidepressant drugs and psychotherapy combined are more effective in treating mood disorders than either treatment alone, but the neurobiological basis of this interaction is unknown. To investigate how antidepressants influence the response of mood-related systems to behavioral experience, we used a fear-conditioning and extinction paradigm in mice. Combining extinction training with chronic fluoxetine, but neither treatment alone, induced an enduring loss of conditioned fear memory in adult animals. Fluoxetine treatment increased synaptic plasticity, converted the fear memory circuitry to a more immature state, and acted through local brain-derived neurotrophic factor. Fluoxetine-induced plasticity may allow fear erasure by extinction-guided remodeling of the memory circuitry. Thus, the pharmacological effects of antidepressants need to be combined with psychological rehabilitation to reorganize networks rendered more plastic by the drug treatment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929964/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929964/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karpova, Nina N -- Pickenhagen, Anouchka -- Lindholm, Jesse -- Tiraboschi, Ettore -- Kulesskaya, Natalia -- Agustsdottir, Arna -- Antila, Hanna -- Popova, Dina -- Akamine, Yumiko -- Bahi, Amine -- Sullivan, Regina -- Hen, Rene -- Drew, Liam J -- Castren, Eero -- DC 003906/DC/NIDCD NIH HHS/ -- DC 009910/DC/NIDCD NIH HHS/ -- R01 DC009910/DC/NIDCD NIH HHS/ -- New York, N.Y. -- Science. 2011 Dec 23;334(6063):1731-4. doi: 10.1126/science.1214592.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sigrid Juselius Laboratory, Neuroscience Center, University of Helsinki, Helsinki, Finland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22194582" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/cytology/drug effects/physiology ; Animals ; Antidepressive Agents, Second-Generation/pharmacology/*therapeutic use ; Anxiety Disorders/*therapy ; *Behavior Therapy ; Brain-Derived Neurotrophic Factor/genetics/metabolism ; Combined Modality Therapy ; Conditioning, Classical ; Excitatory Postsynaptic Potentials/drug effects ; *Extinction, Psychological ; *Fear ; Fluoxetine/pharmacology/*therapeutic use ; Interneurons/drug effects/physiology ; Male ; Memory ; Mice ; Mice, Inbred C57BL ; Nerve Net/drug effects/physiology ; Neuronal Plasticity/*drug effects ; Neurons/cytology/drug effects ; Synaptic Transmission/drug effects
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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