Study of the Role of the Bed Nucleus of the Stria Termialis D1- and D2-Like Dopamine Receptors in Cocaine Self-Administering Rats

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Chiang, Chia-Jung Cindy
Bed Nucleus of the Stria Terminalis , Dopamine , SCH-23390 , Sulpiride , Quinpirole , Cocaine Self-Administration
Previous studies have suggested the importance of the bed nucleus of the stria terminalis (BST) in modulating drug seeking behaviors. With heavy reciprocal projections from the BST to various dopamine rich areas (ventral tegmental area (VTA), nucleus accumbens shell (NAc shell), retrorubral nucleus (RR), periaqueductal gray region (PAG)), BST dopamine receptors are indeed an important part of the highly integrated reward system and thus possess sensitivity to pharmacological rewards. In the present study, the effects of bilateral intracranial injections of the D1- dopamine receptor antagonist SCH-23390 (1.6, 3.2, and 6.4 microgram total bilateral dose) , the D2-dopamine receptor antagonist Sulpiride (3.2 microgram total bilateral dose), and D2- dopamine receptor agonist Quinpirole (3.0 microgram total bilateral dose), administered into the BST immediately prior to self-administration sessions, were examined in both sucrose (180-minute sessions) and cocaine (270-minute sessions) self-administering rats. Injections of SCH-23390 (3.2 & 6.4 microgram) to the cocaine group significantly reduced the final ratio of operant lever responding (0.75 mg/kg/i.v. injection; progressive ratio schedule of reinforcement (PR); timeout 20 sec); there was no effect of SCH-23390 in the sucrose group. Injections of Sulpiride (3.2 microgram) to the cocaine group produced a significant attenuation in the final ratio of operant lever pressing, with no effect in the sucrose group. Injections of Quinpirole, however, resulted in no alternations in both the cocaine and sucrose self-administration group. These results suggest that both D1 and D2 dopamine receptor activation is occurring in the reinforcement of cocaine, with the possibility that D2 receptors are not as highly activated as the D1 receptors. This conclusion further implicates the complexity of the neurobiological factors involved in drug addiction and the essential role of the BST in dopamine-facilitated reward reinforcement.
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