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Differential Response of Central Dopaminergic System in Acute and Chronic Unpredictable Stress Models in Rats

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Abstract

We aimed to evaluate the response of dopaminergic system in acute stress (AS) and chronic unpredictable stress (CUS) by measuring dopamine (DA) levels, its receptor densities in the frontal cortex, striatum, hippocampus, amygdala and orbito-frontal cortex regions of rat brain, and investigated the corresponding behavioral locomotor changes. Involvement of D1 receptor was also examined during AS and CUS using A 68930, a D1 selective agonist. Rats were exposed to AS (single immobilization for 150 min) and CUS (two different stressors for 7 days). AS significantly decreased the DA levels in the striatum and hippocampus, and A 68930 pretreatment significantly reverted these changes. However, in the frontal cortex significantly increased DA levels were remain unchanged following A 68930. CUS led to a decrease of DA levels in the frontal cortex, striatum and hippocampus, which were normalized by A 68930. Saturation radioligand binding assays revealed a significant decrease in the number of D1-like receptors in the frontal cortex during CUS, which were further decreased by A 68930 pretreatment. However, in the striatum and hippocampus, A 68930 pretreatment reduced the CUS induced increase in the number of D1-like receptors. No significant changes were observed in the amygdala and orbito-frontal cortex during AS and CUS, while D2-like receptors were unchanged in all the brain regions studied. Locomotor activity was significantly decreased in both the stress models, A 68930 pretreatment significantly increased stereotypic counts and horizontal activity. Thus, present investigation provide insights into the differential regional response of dopaminergic system during AS and CUS. Further, neurochemical and behavioral effects of D1 agonist pretreatment suggest specific modulatory role of D1 receptor under such stressful episodes.

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Acknowledgments

Authors are deeply grateful to our former colleague Dr. H. K. Singh for help in constructing manuscript and also to ICMR, New Delhi, India for providing financial support.

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Authors and Affiliations

  1. Neuropharmacology Unit, Division of Pharmacology, Central Drug Research Institute, P.B. No. 173, Lucknow, 226001, India

    Naila Rasheed, Ausaf Ahmad, Chandra Prakash Pandey & Gautam Palit

  2. Developmental Toxicology Division, Indian Institute of Toxicology Research, 80 MG Marg, Lucknow, India

    Rajnish Kumar Chaturvedi

  3. Department of Biotechnology, Integral University, Lucknow, 226026, Uttar Pradesh, India

    Mohtashim Lohani

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  1. Naila Rasheed
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  2. Ausaf Ahmad
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Correspondence to Gautam Palit.

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Rasheed, N., Ahmad, A., Pandey, C.P. et al. Differential Response of Central Dopaminergic System in Acute and Chronic Unpredictable Stress Models in Rats. Neurochem Res 35, 22–32 (2010). https://doi.org/10.1007/s11064-009-0026-5

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  • DOI: https://doi.org/10.1007/s11064-009-0026-5

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