Dopaminergic Modulation of Spatial Working Memory in Male Rats: Pre- Experience and Task Dependent Roles of Dopamine D1- and D2-Like Receptors.
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Date
2018-06
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Addis Ababa Universty
Abstract
Dopaminergic Modulation of Spatial Working Memory in Male Rats: Pre-Experience and
Task Dependent Roles of Dopamine D1- and D2-Like Receptors.
Mekite Bezu,
Addis Ababa Univrsity, 2018
The dopaminergic system is known to be involved in working memory processed by several
brain regions like prefrontal cortex (PFC), hippocampus and striatum. Previous studies have
focused on assessing acute effects of drugs on dopamine‟s contribution to working memory in
trained animals. Thus, little is known about effect of repeated application of dopamine targeting
drugs throughout training. The present study aimed to determine effects of repeated
administration of dopaminergic drugs and to delineate the role D1-like and D2-like receptors
(D1R and D2R) subtypes play in spatial working memory modulation and the task -dependent
differences in performance.
Spatial working memory performance in male Sprague-Dawley rats was assessed by repeated
intraperitoneal (IP) application of levodopa (2 or 20 mg/kg) or modafinil (1or 10 mg/kg) through
6 days training or intracerebroventricular (ICV) application of a D1R (SKF81297) and D2R
agonist (Sumanirole) and antagonist (SCH23390, Remoxipride) at low (1μg) and high (5μg) dose
through 3 days of training. Working memory performance test was carried out using T-maze.
The experiment was repeated in a water maze for the most effective ligand to test for the taskdependent
differences in working memory modulation. In addition, cAMP level in the PFC was
assayed for ligands tested in the T-maze.
II
Enhancement in spatial working memory performance was observed at day 3 after levodopa (p<
0.007) but not modafinil administration compared to vehicle-treated animals. Low dose
modafinil treated groups performed better than high dose treated rats and the reverse was true for
levodopa treated rats. In T-maze, the D1R agonist enhanced working memory performance
across training at low dose (p < 0.007), while the high dose induced enhancement only at day1
compared to controls. On the other hand, D1R antagonist showed persistent enhancement of
working memory across training at high dose (p = 0.013), whereas no statistical difference was
observed in low dose. The D2R agonist at both doses was not effective, but low dose of the
D2R antagonist enhanced working memory at day 2.
In water maze task, no significant difference was observed at both doses of the D1R agonist (as
it was the most effective compared to controls in T-maze). However, behavioral performance of
all groups tested in water maze task was different compared to T-maze trained rats. cAMP levels
were not significantly different between D1R agonist and control groups. Higher levels were,
however, obtained in D1R antagonist (low dose) and D2R agonist (high dose) treated rats.
The data collectively support the view that modulation of spatial working memory is optimized
within a limited range of dopaminergic transmission. However, it suggests that these ranges vary
at different time points during spatial training and are also task dependent.
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Keywords
Dopamine, Working memory, T-maze, dopamine receptor D1R, dopamine receptor D2R, water maze.