Kelley A E
Department of Psychiatry, University of Wisconsin-Madison Medical School, Madison 53719, USA.
Ann N Y Acad Sci. 1999 Jun 29;877:71-90. doi: 10.1111/j.1749-6632.1999.tb09262.x.
The nucleus accumbens and its associated circuitry subserve behaviors linked to natural or biological rewards, such as feeding, drinking, sex, exploration, and appetitive learning. We have investigated the functional role of neurotransmitter and intracellular transduction mechanisms in behaviors subserved by the core and shell subsystems within the accumbens. Local infusion of the selective NMDA antagonist, AP-5, into the accumbens core, but not the shell, completely blocked acquisition of a bar-press response for food in hungry rats. This effect was apparent only when infused during the early stages of learning. We have also recently shown that infusion of certain protein kinase inhibitors into the core also impairs learning in the same paradigm. These results suggest that plasticity-related mechanisms within the accumbens core, involving glutamate-linked intracellular second messengers, are important for response-reinforcement learning. In contrast to the core, which primarily connects to somatic motor output systems, the shell is more intimately linked to viscero-endocrine effector systems. We have shown that both AMPA and GABA receptors within the medial shell (but not the core) are critically involved in controlling the brain's feeding pathways, via activation of the lateral hypothalamus (LH). This effect is blocked by local inhibition of the LH in double-cannulae experiments and also strongly and selectively activates Fos expression in the LH. These results provide a newly emerging picture of the differentiated functions of this forebrain region and suggest an integrated role in the elaboration of adaptive motor actions.
伏隔核及其相关神经回路参与与自然或生物奖励相关的行为,如进食、饮水、性行为、探索和食欲学习。我们研究了神经递质和细胞内转导机制在伏隔核核心和壳子系统所支持的行为中的功能作用。向伏隔核核心而非壳部局部注入选择性NMDA拮抗剂AP-5,完全阻断了饥饿大鼠为获取食物而进行的压杆反应的习得。这种效应仅在学习早期注入时才明显。我们最近还表明,向核心注入某些蛋白激酶抑制剂也会损害同一范式中的学习。这些结果表明,伏隔核核心内与可塑性相关的机制,涉及谷氨酸连接的细胞内第二信使,对反应强化学习很重要。与主要连接到躯体运动输出系统的核心不同,壳部与内脏-内分泌效应系统联系更为紧密。我们已经表明,内侧壳部(而非核心)内的AMPA和GABA受体通过激活下丘脑外侧区(LH),在控制大脑的进食途径中起关键作用。在双套管实验中,这种效应被LH的局部抑制所阻断,并且还强烈且选择性地激活了LH中的Fos表达。这些结果提供了这个前脑区域分化功能的新图景,并表明其在适应性运动行为的精细调节中起综合作用。