Rewarding Actions of Phencyclidine and Related Drugs in Nucleus Accumbens Shell and Frontal Cortex
Rewarding Actions of Phencyclidine and Related Drugs in Nucleus Accumbens Shell and Frontal Cortex
复制标题
DOI：
10.1523/jneurosci.16-09-03112.1996
复制
发表时间：
1996-05
期刊：
影响因子：
--
通讯作者：
W. Carlezon;R. Wise
中科院分区：
文献类型：
--
作者：
W. Carlezon;R. Wise
当直接将苯环己哌啶（PCP）微量注射到丘脑腹内侧（壳）区域时，大鼠学会了按压，这表明该药物在该区域具有直接的奖励作用。当向同一区域微量注射地佐环平（MK-801）或3-（（±）2-羧基哌嗪-4基）丙基-1-磷酸（CPP）（已知阻断NMDA受体功能但不阻断多巴胺摄取的药物）时，不同组的大鼠学会了按压。每种药物是无效的或显着不太有效时，注射在一个稍微更背侧和外侧的网站在核心的延髓。PCP、MK-801或CPP直接进入丘脑核的自我给药并没有被多巴胺拮抗剂舒必利的联合输注所改变，舒必利的剂量有效地阻断了多巴胺摄取抑制剂诺米芬新的颅内自我给药，这表明NMDA受体拮抗剂的奖励作用不是多巴胺依赖性的。当PCP、MK-801和CPP分别被直接微量注射到额叶皮质时，大鼠也会养成按下按钮的习惯，额叶皮质是以前与可卡因而不是诺米芬辛的奖励作用相关的区域。因此，脑桥核和额叶皮层是PCP和相关药物的奖励特性的潜在底物，这些药物破坏NMDA受体功能的能力似乎足以解释它们的奖励作用。当考虑到独立的证据，目前的结果表明，药物奖励模型中的关键事件是抑制中棘神经元的延髓核。
Rats learned to lever-press when such behavior was reinforced by microinjections of phencyclidine (PCP) directly into the ventromedial (shell) region of nucleus accumbens, indicating that the drug has direct rewarding actions in that region. Separate groups of rats learned to lever-press when reinforced with microinjections of dizocilpine (MK-801) or 3-((±)2-carboxypiperazin-4yl)propyl-1-phosphate (CPP), drugs known to block NMDA receptor function but not dopamine uptake, into the same region. Each drug was ineffective or markedly less effective when injected at a slightly more dorsal and lateral site in the core of nucleus accumbens. Self-administration of PCP, MK-801, or CPP directly into nucleus accumbens was not altered by co-infusion of a dose of the dopamine antagonist sulpiride that effectively blocked intracranial self-administration of the dopamine uptake inhibitor nomifensine, suggesting that the rewarding actions of the NMDA receptor antagonists are not dopamine-dependent. Rats also developed lever-pressing habits when PCP, MK-801, and CPP were each microinjected directly into frontal cortex, a region previously associated with the rewarding actions of cocaine but not nomifensine. Thus nucleus accumbens and frontal cortex are each potential substrates for the rewarding properties of PCP and related drugs, and the ability of these drugs to disrupt NMDA receptor function seems sufficient to account for their rewarding actions. When considered with independent evidence, the present results suggest a model of drug reward within which the critical event is inhibition of medium spiny neurons in nucleus accumbens.