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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