Microinjections of phencyclidine (PCP) and related drugs into nucleus accumbens shell potentiate medial forebrain bundle brain stimulation reward

Microinjections of phencyclidine (PCP) and related drugs into nucleus accumbens shell potentiate medial forebrain bundle brain stimulation reward
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DOI:
10.1007/s002130050151
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发表时间:
1996-12-01
期刊:
影响因子:
3.4
通讯作者:
Wise, RA
Wise, RA
中科院分区:
医学3区
文献类型:
--
作者:
Carlezon, WA;Wise, RA

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在大鼠延髓腹内侧核微量注射苯环利定(PCP)可增强下丘脑外侧脑刺激的奖赏效应。诺米芬辛也有类似的作用,它与PCP一样具有阻断多巴胺摄取的能力,从而提高突触多巴胺水平,但与PCP不具有阻断NMDA受体的能力。地佐环平(MK-801)和[3-((+/-)2-羧基哌嗪-4-基)丙基-1-膦酸酯](CPP)也观察到类似的作用,它们与PCP具有阻断NMDA受体但不阻断多巴胺摄取的能力。因此,PCP作为多巴胺摄取抑制剂和NMDA受体拮抗剂的特性似乎都能够在该脑区产生与奖励相关的作用。这两种PCP作用的共同点是减少中型棘状神经元的输出;这些神经元被来自前额叶皮层的谷氨酸投射紧张性激活(PCP阻断这种激活源),并被来自腹侧被盖区的多巴胺能投射紧张性抑制(PCP Au这种抑制)。
Microinjections of phencyclidine (PCP) into the ventro-medial portion of nucleus accumbens in rats potentiated the rewarding impact of lateral hypothalamic brain stimulation. Similar effects were found with nomifensine, which shares with PCP the ability to block dopamine uptake and thus elevate synaptic dopamine levels but does not share with PCP the ability to block NMDA receptors. Similar effects were also seen with dizocilpine (MK-801) and [3-((+/-)2-carboxypiperazin-4-yl)propyl-1-phosphonate] (CPP), which share with PCP the ability to block NMDA receptors but not to block dopamine uptake. Thus PCP's properties as a dopamine uptake inhibitor and as an NMDA receptor antagonist each appear capable of producing reward-related actions in this brain region. The common denominator of these two PCP actions is decreased output of medium spiny neurons; these neurons are tonically activated by a glutamate projection from prefrontal cortex (PCP blocks this source of activation) and are tonically inhibited by a dopaminergic projection from the ventral tegmental area (PCP au this inhibition).