Reynolds Sheila M, Berridge Kent C
Department of Psychology, University of Michigan, Ann Arbor, MI 48109-1109, USA.
Eur J Neurosci. 2003 May;17(10):2187-200. doi: 10.1046/j.1460-9568.2003.02642.x.
This study demonstrates that microinjection of an AMPA/kainate glutamate antagonist elicits motivated fear and feeding behaviour mapped along rostrocaudal gradients of positive-to-negative valence in nucleus accumbens shell (similar to rostrocaudal shell gradients recently reported for GABA agonist microinjections). Rats received rostral or caudal microinjections of the glutamate AMPA/kainate receptor antagonist DNQX (0, 50, 450 or 850 ng in 0.5 micro L) or the NMDA receptor antagonist MK-801 (0, 0.5, 1 or 2 micro g in 0.5 micro L), into medial accumbens shell prior to behavioural tests for fear, feeding or conditioning of place preference or avoidance. Another group received rostral or caudal microinjections of DNQX in nucleus accumbens core. Rostral shell DNQX microinjections potently increased appetitive food intake and established only weak conditioned place avoidance. Caudal shell DNQX microinjections elicited defensive treading behaviour, caused rats to defensively bite the experimenter and emit fearful distress vocalizations when handled, and established strong conditioned place avoidance. By contrast, no rostrocaudal gradients of motivational bivalence were produced by microinjections of the glutamate AMPA/kainate receptor antagonist DNQX into the core, or by microinjections of the NMDA antagonist MK-801 into the shell. Our results indicate that appetitive and aversive motivation is carried in anatomically differentiated channels by mesocorticolimbic glutamate signals to microcircuits in the medial shell. Hyperpolarization of local shell ensembles by AMPA/kainate glutamate receptor blockade elicits fear and feeding behaviours mapped along distinct positive-to-negative rostrocaudal gradients.
本研究表明,向伏隔核壳部微量注射AMPA/海人酸谷氨酸拮抗剂会引发动机性恐惧和摄食行为,这些行为沿伏隔核壳部从正价到负价的前后梯度分布(类似于最近报道的向伏隔核壳部微量注射GABA激动剂时的前后壳部梯度)。在进行恐惧、摄食、位置偏好或回避条件化行为测试之前,给大鼠在内侧伏隔核壳部进行AMPA/海人酸受体拮抗剂DNQX(0、50、450或850 ng于0.5 μL中)或NMDA受体拮抗剂MK-801(0、0.5、1或2 μg于0.5 μL中)的吻端或尾端微量注射。另一组大鼠在伏隔核核心进行DNQX的吻端或尾端微量注射。吻端壳部微量注射DNQX可显著增加食欲性食物摄入量,且仅产生微弱的条件性位置回避。尾端壳部微量注射DNQX会引发防御性踏步行为,导致大鼠在被处理时防御性地咬实验者并发出恐惧的痛苦叫声,并产生强烈的条件性位置回避。相比之下,向伏隔核核心微量注射谷氨酸AMPA/海人酸受体拮抗剂DNQX,或向伏隔核壳部微量注射NMDA拮抗剂MK-801,均未产生动机双价性的前后梯度。我们的结果表明,中脑皮质边缘谷氨酸信号通过解剖学上有差异的通道将食欲性和厌恶性动机传递至内侧壳部的微回路。通过AMPA/海人酸谷氨酸受体阻断使局部壳部神经元超极化,会引发沿不同的从正价到负价的前后梯度分布的恐惧和摄食行为。