| Abstract No.: | A-G1193 |
| Country: | Canada |
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| Title: | DOPAMINE IN THE BED NUCLEUS OF THE STRIA TERMINALIS IS CRITICAL IN THE REINFORCEMENT PRODUCED BY NATURAL OR PHARMACOLOGICAL REWARDS |
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| Authors/Affiliations: | 1 Meredith J. Kuipers*, 2 Adam Schizkoske, 3 Dasha V. Ianovskaia, 4 Eric C. Dumont; Queen's University, Department of Anesthesiology & Centre for Neurosciences Studies, Kingston, ON, Canada |
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| Content: | Objective: Dopamine is a key neurotransmitter in natural reward pathways and has been implicated in goal-oriented behaviours. Dysfunctions of dopaminergic systems can lead to several pathologies including 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 receives a dense dopaminergic input from the VTA, though the role of dopamine in the BST is currently unknown. The goal of this study was to determine whether pharmacological manipulation of D1 and D2 dopamine receptors in the BST altered operant learning towards natural or pharmacological rewards.
Methods: Twenty Long-Evans rats were chronically implanted with bilateral 22-gauge cannula placed in the dorsal part of the anterior BST (antBST). Fourteen rats were further implanted with an indwelling catheter in the left jugular vein for intravenous (IV) self-administration of cocaine-HCl (0.75mg/kg per 0.1ml injections, pH 7.4). Rats were given daily access to an operant chamber and tested for sucrose pellet self-delivery or IV cocaine self-administration. After three days of stable pressing (40 presses/session) on a fixed-ratio schedule of reinforcement (one lever-press = one reward), the rats were tested on a progressive-ratio (PR) schedule of reinforcement. The dependent variable was breakpoint (60 minutes without further reward) on the PR schedule of reinforcement.
Results: A dose-dependent reduction of the breakpoint was recorded following bilateral intra-antBST microinjections of the D1 dopamine receptor antagonist SCH-23390 (0.8-1.6 µg/0.5µl/per side), for both sucrose pellet delivery and cocaine IV self-administration on a PR schedule of reinforcement. Similarly, inactivation of the antBST with the GABAA agonist muscimol (0.5µg/0.5µl/per side) significantly reduced breakpoint for both sucrose pellet delivery and intravenous cocaine self-administration. Conversely, intra-antBST microinjections of the selective D2 dopamine receptor antagonist sulpiride (1.6µg/0.5µl/per side) did not change sucrose or cocaine taking behaviours.
Conclusion: Our study demonstrates that the BST is an important neural centre where dopamine contributes to the reinforcing properties of natural and pharmacological rewards. These results strengthen the current understanding of the neurobiological basis of goal-directed behaviours, which could lead to improvement in the treatment and management of addiction.
Supported by CIHR (MOP-79277) and The J.P. Bickell Foundation.
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