Developmental effects of early-life stress on dopamine D2 receptor and proteins involved in noncanonical D2 dopamine receptor signaling pathway in the prefrontal cortex of male rats
Author:
Mahmoodkhani Maryam1, Ghasemi Maedeh2, Derafshpour Leila1, Amini Mohammad3, Mehranfard Nasrin1
Affiliation:
1. Neurophysiology Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences , Urmia , Iran 2. Department of Physiology , School of Medicine, Isfahan University of Medical Sciences , Isfahan , Iran 3. School of Medicine, Shahroud University of Medical Sciences , Shahroud , Iran
Abstract
Abstract
Objectives
Dopamine neurotransmission is implicated in multiple neuropsychiatric disorders, most strikingly in Parkinson’s disease, bipolar disorder, attention-deficit hyperactivity disorder and schizophrenia. In addition to canonical pathway, D2-receptor (D2R) exerts some of its biological actions through regulating the activity of Akt and GSK3, which in turn were found to be altered in several psychiatric illnesses. The present study examined the impacts of maternal separation, an early-life stress model which has been associated with disturbed neurodevelopment and appearance of many psychiatric disorders, on developmental changes in dopamine concentration and the expression of D2Rs, Akt and GSK-3β in the medial prefrontal cortex (PFC; a key target of stress) in adolescent and young adult male rats.
Methods
Maternal separation was performed 3 h per day from postnatal days 2 to 11. The PFC protein and dopamine contents were determined using western blotting analysis and Eliza, respectively.
Results
Results indicated long-term increases in the prefrontal dopamine levels in stressed adolescent and young adult male rats, accompanied by significant downregulation of D2R as well as upregulation of p-Akt and GSK-3β contents in stressed adolescence compared to controls, with all protein levels that returned to control values in stressed adult rats.
Conclusions
Our findings suggest that early-life stress differentially modulates prefrontal D2R/Akt/GSK-3β levels during development. Since adolescence period is susceptible to the onset of specific mental illnesses, disruption of noncanonical components of D2R signaling during this critical period may have an important role in programming neurobehavioral phenotypes in adulthood and manipulations influencing Akt/GSK-3β pathway may improve the expression of specific dopamine-related behaviors and the effects of dopaminergic drugs.
Publisher
Walter de Gruyter GmbH
Subject
Complementary and alternative medicine
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