Amphetamine activation of hippocampal drive of mesolimbic dopamine neurons: A mechanism of behavioral sensitization
Amphetamine activation of hippocampal drive of mesolimbic dopamine neurons: A mechanism of behavioral sensitization
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DOI：
10.1523/jneurosci.1582-08.2008
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发表时间：
2008-07-30
影响因子：
5.3
通讯作者：
Grace, Anthony A.
中科院分区：
文献类型：
--
作者：
Lodge, Daniel J.;Grace, Anthony A.
反复服用精神刺激剂会导致对随后的药物挑战的行为反应增强。这种行为敏感化被提出用来模拟在人类精神刺激性药物滥用者中观察到的日益增长的药物渴望。利用已鉴定的腹侧被盖区多巴胺(DA)神经元的细胞外记录，我们报告了苯丙胺致敏的大鼠表现出激活的腹侧海马神经元放电，并且与生理盐水处理的大鼠相比，自发激活的DA神经元的数量显著增加。此外，腹侧海马区的TTX失活使DA神经元的活动恢复到控制水平，也阻断了运动敏化的表达。综上所述，我们认为对精神刺激剂药物的行为敏感化至少部分归因于腹侧海马-伏隔核通路的持续激活，从而导致紧张性DA神经元放电的增加，使其对随后的精神刺激剂药物产生异常高的反应。
The repeated administration of psychostimulants induces an enhanced behavioral response to a subsequent drug challenge. This behavioral sensitization is proposed to model the increased drug craving observed in human psychostimulant abusers. Using in vivo extracellular recordings from identified ventral tegmental area dopamine (DA) neurons, we report that amphetamine-sensitized rats display an activation of ventral hippocampal neuron firing and a significantly greater number of spontaneously active DA neurons compared with saline-treated rats. Moreover, TTX inactivation of the ventral hippocampus restores DA neuron activity to control levels and also blocks the expression of locomotor sensitization. Taken as a whole, we propose that behavioral sensitization to psychostimulant drugs is attributable, at least in part, to persistent activation of the ventral hippocampus-nucleus accumbens pathway, with the resultant increase in tonic DA neuron firing enabling an abnormally higher response to subsequent psychostimulant administration.