Sub-region specific contribution of the ventral hippocampus to drug context-induced reinstatement of cocaine-seeking behavior in rats.
Sub-region specific contribution of the ventral hippocampus to drug context-induced reinstatement of cocaine-seeking behavior in rats.
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DOI：
10.1016/j.neuroscience.2010.09.032
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发表时间：
2010-12-15
期刊：
影响因子：
3.3
通讯作者：
Fuchs RA
中科院分区：
文献类型：
--
作者：
Lasseter HC;Xie X;Ramirez DR;Fuchs RA
腹侧海马（VH）在线索诱导和可卡因引发的可卡因寻求恢复中起着关键作用。VH的亚区域对介导药物环境诱导的恢复的脑复发回路的元件做出不同的预测。因此，VH也可能以分区域特有的方式对这种形式的可卡因寻求起到关键作用。因此，本研究评估的假设，腹侧海马适当（VHP）的功能失活-但不是齿状回（DG）-损害可卡因寻求引起的重新暴露于药物配对的环境背景。在不同的环境背景（可卡因配对背景）中训练大鼠杠杆按压以进行未发出信号的静脉内可卡因输注（0.15 mg/输注），然后在明显不同的背景（消退背景）中进行消退训练。随后，可卡因寻求行为（即，非增强主动杠杆反应）在先前可卡因配对的背景或消退背景中进行评估。在每次测试之前，大鼠接受双侧微量输注γ-氨基丁酸（GABA）激动剂混合物、巴氯芬+蝇蕈醇（BM：1.0/.01 mM）或溶媒至VHp、DG或背侧海马后部（pDH;额外VH对照）。暴露于先前可卡因配对的背景下，但不是灭绝的背景下，恢复了车辆预处理后熄灭的可卡因寻求行为。BM预处理给予VHp，但不是DG或pDH，显着减弱药物上下文诱导的可卡因寻求。这些结果表明，VH有助于药物上下文诱导的可卡因寻求在一个特定的子区域的方式，与VHP的功能完整性是必要的药物配对的环境刺激，维持刺激控制目标导向的行为的记忆或动机方面。
The ventral hippocampus (VH) plays critical roles in cue-induced and cocaine-primed reinstatement of cocaine seeking. Subregions of the VH make distinct projections to elements of the brain relapse circuitry that mediate drug context-induced reinstatement. Thus, the VH may also critically contribute to this form of cocaine seeking in a subregion-specific manner. Accordingly, this study evaluated the hypothesis that functional inactivation of the ventral hippocampus proper (VHp) – but not of the dentate gyrus (DG) – impairs cocaine seeking elicited by re-exposure to a drug-paired environmental context. Rats were trained to lever press for un-signaled intravenous cocaine infusions (0.15 mg/infusion) in a distinct environmental context (cocaine-paired context) followed by extinction training in a distinctly different context (extinction context). Subsequently, cocaine-seeking behavior (i.e., non-reinforced active lever responding) was assessed in either the previously cocaine-paired context or the extinction context. Rats received bilateral microinfusions of the gamma-aminobutyric acid (GABA) agonist cocktail, baclofen+muscimol (BM: 1.0/.01mM), or vehicle into the VHp, DG, or the posterior dorsal hippocampus (pDH; extra-VH control) immediately before each test session. Exposure to the previously cocaine-paired context, but not the extinction context, reinstated extinguished cocaine-seeking behavior following vehicle pretreatment. BM pretreatment administered into the VHp, but not the DG or pDH, significantly attenuated drug context-induced cocaine seeking. These results indicate that the VH contributes to drug context-induced cocaine seeking in a subregion-specific manner, with the functional integrity of the VHp being necessary for memory or motivational aspects of drug-paired environmental stimuli that sustain stimulus control over goal-directed behavior.
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影响因子：
16.2
作者：
Fanselow, Michael S.;Dong, Hong-Wei
通讯作者：
Dong, Hong-Wei
影响因子：
3.4
作者：
EHRMAN, RN;ROBBINS, SJ;OBRIEN, CP
通讯作者：
OBRIEN, CP
影响因子：
--
作者：
Kilts, CD;Schweitzer, JB;Drexler, KPG
通讯作者：
Drexler, KPG
影响因子：
3.3
作者：
JOHNSON, LR;AYLWARD, RLM;TOTTERDELL, S
通讯作者：
TOTTERDELL, S
影响因子：
3.3
作者：
KELLEY, AE;DOMESICK, VB
通讯作者：
DOMESICK, VB