| Abstract No.: | A-B1053 |
| Country: | Canada |
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| Title: | BIDIRECTIONAL MODULATION OF EXCITATORY TRANSMISSION BY DOPAMINE IN THE BED NUCLEUS OF THE STRIA TERMINALIS |
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| Authors/Affiliations: | 1 Julian Mackenzie-Feder, 1 Nicole J. Bailey, 1 Eric C. Dumont;
1 Queen's University, Kingston, ON, Canada |
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| Content: | Objectives: Dopamine is a key neurotransmitter in goal-oriented behaviors and dysfunctions of dopaminergic systems contribute to pathologies such as addiction. The midbrain ventral tegmental area (VTA) is rich in dopamine neurons and projects to several cortical and subcortical structures such as the prefrontal cortex, the amygdala, the striatum and the hippocampus. The bed nucleus of the stria terminalis (BST) also has a dense dopaminergic input that has received very little attention. However, our laboratory recently demonstrated (see Kuipers et al.) that dopamine in the BST is critical for operant behaviours towards natural (sucrose) or pharmacological (cocaine) rewards. The goal of the present study was to determine the synaptic mechanisms by which dopamine in the BST contribute to goal-directed behaviours.
Methods: Whole-cell voltage clamp recordings were made from rat brain slices containing the anterior region of the BST (antBST). Recordings were made from neurons located in the dorsolateral region of the antBST, site of the densest dopaminergic innervation to the BST. AMPA glutamatergic receptor-mediated excitatory postsynaptic currents (EPSCs) were electrically evoked by local fiber stimulation in the presence of the GABAA antagonist picrotoxin (100然). Each electrical stimulus consisted of two pulses (50msec interval) at 0.1 Hz in order to obtain paired-pulse ratios (PPR) of the evoked EPSCs. Spontaneous miniature AMPA EPSCs were recorded in the presence of the voltage-gated sodium channel blocker tetrodotoxin (0.5然). The effect of bath application of dopamine or dopaminergic agonists and antagonists on the amplitude of evoked or miniature EPSC were measured.
Results: Dopamine (10然) or the specific D1 dopamine receptor agonist SKF (1然) increased the amplitude of evoked AMPA EPSCs. Whilst increasing the concentration of dopamine to 30然 did not change the amplitude of evoked AMPA EPSCs, dopamine 100然 or the selective D2 dopamine receptor agonist quinpirole (1然) reduced the amplitude of the evoked EPSCs by 50%. Finally, dopamine at low concentration (10-30然) did not change the PPR suggesting a postsynaptic localization of D1 receptors. Conversely, 100然 dopamine increased the PPR and reduced the frequency of miniature AMPA EPSCs suggesting a presynaptic effect on glutamate release.
Conclusion: Our study demonstrate that dopamine modulate excitatory transmission in the BST. The direction of the modulation depends both on the concentration of dopamine and whether dopamine activates D1 or D2 receptors in the BST. These observations might represent the mechanism by which dopamine in the BST contribute to goal-directed behaviours.
Supported by CIHR (MOP-79277) and The J.P. Bickell Foundation.
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