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Neuroanatomical, Biochemical, and Functional Modifications in Brain Induced by Treatment with Antidepressants

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Abstract

Depression is a psychosomatic disorder. The pharmacological treatment of depression has been based on the pathophysiology of deficiency in monoamines, mainly serotonin and noradrenaline. All approved antidepressants designed to enhance central monoaminergic tone possess many limitations such as 2 to 5 weeks delay in response, a limited clinical efficacy, and severe side effects. Since the pathophysiological aberrations associated to depression go beyond monoamines, the development of better antidepressants would depend on the identification and understanding of new cellular targets. The pharmacological studies of antidepressants, however, indicate the involvement of the blockade of neuronal uptake systems for norepinephrine and serotonin (5-hydroxytryptamine) including receptors for neurotransmitters. Many preclinical studies have suggested that hippocampus containing abundant agonists such as5-HT1A and 5-HT4 receptor subtypes in the dentate gyrus (DG) is critically involved in the mechanism of action of antidepressants. DG being a part of hippocampus possibly contributes to the brain functions such as formation of new sporadic memories. It is reported that antidepressants cause significant alterations in the structure and function of different brain regions in order to finally lead to their therapeutic effects. This review presents an overview of structural changes in the brain during depression; different neurobiological theories and novel drug development; strategy of augmentation with combinatorial therapy; receptors and targets of actions of antidepressants; and involvement of key signaling factors in the regulation of depression, pharmacology, metabolism, and the underlying principles involved in displaying how the application of antidepressants modulates the structure and function of the brain.

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Acknowledgements

The authors thank UGC-SAP and DST-FIST for providing facilities to conduct research. The authors also thank the Deanship of Scientific Research and RSSU at King Saud University for their technical support.

Funding

Khushboo is thankful to UGC-New Delhi for financial support in the form of a fellowship. BS is grateful to UPCST-Lucknow for financial support in the form of a Research Grant. M.d.L.P. acknowledges the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020, financed by national funds through the FCT/MCTES and when appropriate co-financed by FEDER under the PT2020 partnership agreement.

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  1. Department of Biochemistry, University of Allahabad, Allahabad, 211002, India

    Khushboo & Bechan Sharma

  2. Department of Biochemistry, King Saud University, Riyadh, Saudi Arabia

    Nikhat J. Siddiqi

  3. Department of Medical Sciences, CICECO-Aveiro Institute of Materials &, University of Aveiro, 3810-193, Aveiro, Portugal

    Maria de Lourdes Pereira

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Khushboo searched the concerned information on the topic from various sources, organized the information systematically, made proper analysis, and presented first draft of the manuscript. BS conceived the idea, decided different aspects of the topic, and added the relevant contents in the manuscript. NJS and MLP critically reviewed the manuscript and provided their valuable inputs.

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Khushboo, Siddiqi, N.J., de Lourdes Pereira, M. et al. Neuroanatomical, Biochemical, and Functional Modifications in Brain Induced by Treatment with Antidepressants. Mol Neurobiol 59, 3564–3584 (2022). https://doi.org/10.1007/s12035-022-02780-z

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