Acute administration of SB-277011A, NGB 2904, or BP 897 inhibits cocaine cue-induced reinstatement of drug-seeking behavior in rats:: Role of dopamine D3 receptors
Acute administration of SB-277011A, NGB 2904, or BP 897 inhibits cocaine cue-induced reinstatement of drug-seeking behavior in rats:: Role of dopamine D3 receptors
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作者：
Gilbert, JG;Newman, AH;Xi, ZX
最近的研究表明，新型多巴胺 (DA) D-3 受体拮抗剂 SB-277011A 和 NGB 2904 可抑制可卡因和/或压力诱导的寻药行为恢复。本研究试图确定 SB-277011A、NGB 2904 或 BP-897（混合 D-3 激动剂/拮抗剂）是否同样抑制可卡因相关线索诱导的寻药行为恢复。朗-埃文斯大鼠被允许自行注射可卡因。每次可卡因输注都配有离散的条件提示光和音调。随后，在没有可卡因和可卡因相关线索的情况下，寻求药物（即按下杠杆）行为就会消失。然后对大鼠进行了线索诱导的药物寻求恢复测试。我们发现与可卡因相关的线索会引起杠杆按压的强烈恢复。与媒介物治疗的动物相比，急性腹膜内 (i.p.) 施用 SB-277011A（6、12 或 24 mg/kg）对提示诱导的药物寻求行为恢复产生剂量依赖性抑制，分别抑制 35%、65% 和 85%。急性腹腔注射与媒介物处理的动物相比，给予 NGB 2904（0.1、1.0 或 5.0 mg/kg）分别对提示诱导的恢复产生 45%、30% 和 70% 的抑制。急性腹腔注射给予 0.1 或 1 mg/kg BP 897 不会对提示诱导的恢复产生显着影响，而 3 mg/kg 的剂量对提示诱导的恢复产生 70% 的抑制。这些发现与之前的数据相结合，表明 DA D3 受体拮抗作用可能是 SB-277011A 和 NGB 2904 对可卡因提示诱导的恢复的抑制作用的基础，而 BP 897 的作用可能涉及 D-3 和非 D-3 受体机制。 2005 年出版 Wiley-Liss, Inc.
Recent studies have shown that the novel dopamine (DA) D-3 receptor antagonists SB-277011A and NGB 2904 inhibit cocaine- and/or stress-induced reinstatement of drug-seeking behavior. The present study sought to determine if SB-277011A, NGB 2904, or BP-897 (a mixed D-3 agonist/antagonist) similarly inhibit cocaine-associated cue-induced reinstatement of drug-seeking behavior. Long-Evans rats were allowed to self-administer cocaine. Each cocaine infusion was paired with discrete conditioned cue-light and tone. Subsequently, drug-seeking (i.e., lever-pressing) behavior was extinguished in the absence of cocaine and cocaine-associated cues. Rats were then tested for cue-induced reinstatement of drug-seeking. We found that cocaine-associated cues evoked robust reinstatement of lever-pressing. Acute intraperitoneal (i.p.) administration of SB-277011A (6, 12, or 24 mg/kg) produced a dose-dependent inhibition of cue-induced reinstatement of drug-seeking behavior by 35, 65, and 85%, respectively, compared to vehicle-treated animals. Acute i.p. administration of NGB 2904 (0.1, 1.0, or 5.0 mg/kg) produced a 45, 30, and 70% inhibition of cue-induced reinstatement, respectively, compared to vehicle-treated animals. Acute i.p. administration of either 0.1 or 1 mg/kg of BP 897 did not produce a significant effect on cue-induced reinstatement, whereas a dose of 3 mg/kg produced a 70% inhibition of cue-induced reinstatement. These findings, combined with previous data, suggest that DA D3 receptor antagonism may underlie the inhibitory effects of SB-277011A and NGB 2904 on cocaine cue-induced reinstatement, while the effects of BP 897 may involve D-3 and non-D-3 receptor mechanisms. Published 2005 Wiley-Liss, Inc.