Early life stress influences basal ganglia dopamine receptors and novel object recognition of adolescent and adult rats

• Published in: IBRO neuroscience reports Vol. 12; pp. 342 - 354
• Main Authors: Sinani, Ada, Vassi, Andriana, Tsotsokou, Giota, Nikolakopoulou, Maria, Kouvelas, Elias D., Mitsacos, Ada
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-06-2022; Elsevier
• Subjects: Dopamine receptors; Maternal separation; Neonatal handling; Novel object recognition; Nucleus accumbens; Research Paper; Striatum; Nucleus accumbens; Striatum; Neonatal handling; Novel object recognition; Maternal separation; Dopamine receptors
• ISSN: 2667-2421; 2667-2421
• DOI: 10.1016/j.ibneur.2022.04.008

Environmental stimuli in early life are recognized to affect brain development and behavior. Mother-pup interaction constitutes a determinant stimulus during this critical period. It is known that the dopaminergic system undergoes significant reorganization during adolescence and that dopamine receptors are involved in recognition memory. Based on the above, we examined the effects of brief and prolonged maternal separation during the neonatal period (15 or 180 min daily) on basal ganglia dopamine receptors and on the behavior in the novel object recognition task of adolescent and adult male rats. Using the NOR task, we observed that the discrimination index (DI) was decreased in rats with brief maternal separations independent of age. Using receptor autoradiography, we observed that brief maternal separation induced decreases in D1, D2 and D4 receptor binding levels in adult basal ganglia nuclei, while prolonged maternal separation induced increases in D1 receptor binding levels in caudate - putamen (CPu) of adolescent rats. With immunoblotting experiments, we found decreases in D1 and increases in D2 total protein levels in CPu of adult rats with prolonged maternal separations. Α positive correlation was observed between DI and D1 binding levels in CPu, internal globus pallidus and substantia nigra, and D2 binding levels in nucleus accumbens core in adult rats, using the Pearson correlation coefficient. Our results indicate that the long-lasting effects of neonatal mother-offspring separation on dopamine receptors depend on the duration of maternal separation and age and that this early life experience impairs recognition memory in adolescent and adult rats. Furthermore, the present results suggest that modulation of striatal dopamine receptors might underlie the reduced recognition memory of adult rats with brief neonatal maternal separations.
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•PMS promotes increase in D1 dopamine receptor binding levels in adolescent striatum.•BMS promotes decreases in D1, D2 and D4 receptor binding levels in adult striatum.•PMS promotes decrease in D1 and increase in D2 protein expression in adult striatum.•BMS promotes decrease in discrimination index of NOR task independent of age.•Striatal D1 receptor binding levels are strongly correlated with discrimination index.