Guarraci F A, Frohardt R J, Kapp B S
Department of Psychology, University of Vermont, Burlington, VT 05405, USA.
Brain Res. 1999 May 8;827(1-2):28-40. doi: 10.1016/s0006-8993(99)01291-3.
The amygdala has long been implicated in conditioned fear. The mesencephalic dopaminergic system provides a rich innervation to the amygdala [J.H. Fallon, P. Ciofi, Distribution of monoamines within the amygdala, in: J.P. Aggleton (Ed.), The Amygdala: Neurobiological Aspects of Emotion, Memory and Mental Dysfunction, Wiley, New York, 1992, pp. 97-114; L.J. Freedman, M.D. Cassell, Distribution of dopaminergic fibers in the central division of the extended amygdala of the rat. Brain Research 633 (1994) 243-252; E. Asan, The catecholaminergic innervation of the rat amygdala. Advances in Anatomy Embryology and Cell Biology 142 (1996) 1-107]. Specific activation of the mesoamygdaloid dopaminergic system has been reported to occur in response to conditioned fear-arousing stimuli [M.L. Coco, C.M. Kuhn, T.D. Ely, C.D. Kilts, Selective activation of mesoamygdaloid dopamine neurons by conditioned stress: attenuation by diazepam. Brain Research 590 (1992) 39-47] suggesting that dopamine release in the amygdala may contribute to the acquisition and/or expression of conditioned fear. Using a 2x2 factorial design, Experiment 1A investigated the effects of bilateral intra-amygdaloid infusions of the selective D1 receptor antagonist, SCH 23390 (2.0 microgram 0.5 microliter-1 side-1), on the acquisition and expression of Pavlovian conditioned fear measured by freezing to acoustic and background contextual stimuli. Infusions of SCH 23390 prior to acquisition training, prior to retention testing or prior to both significantly attenuated conditioned freezing during retention testing. Experiment 1B investigated the dose-dependent effects of pre-training infusions of SCH 23390 (0.5, 1.0 and 2.0 microgram) on conditioned fear. Pre-training infusions of SCH 23390 dose-dependently attenuated conditioned freezing during retention testing. Experiment 2A investigated the effects of bilateral infusions of the selective D1 receptor agonist, SKF 82958 (2.0 microgram 0.5 microliter-1 side-1) on the acquisition and expression of conditioned fear. Infusions of SKF 82958 prior to training facilitated conditioned freezing during retention testing. Experiment 2B investigated the dose-dependent effects of pre-training infusions of SKF 82958 (1.0, 2.0 and 4.0 microgram) on conditioned fear. Pre-training infusions of SKF 82958 dose-dependently facilitated conditioned freezing during retention testing. In conclusion, these results suggest that dopamine transmission within the amygdala contributes to the acquisition and expression of Pavlovian fear conditioning.
杏仁核长期以来一直被认为与条件性恐惧有关。中脑多巴胺能系统为杏仁核提供了丰富的神经支配[J.H.法伦，P.乔菲，杏仁核内单胺的分布，载于：J.P.阿格利顿（编），《杏仁核：情绪、记忆和精神功能障碍的神经生物学方面》，威利出版社，纽约，1992年，第97 - 114页；L.J.弗里德曼，M.D.卡塞尔，多巴胺能纤维在大鼠扩展杏仁核中央区的分布。《脑研究》633（1994年）243 - 252页；E.阿桑，大鼠杏仁核的儿茶酚胺能神经支配。《解剖学、胚胎学和细胞生物学进展》142（1996年）1 - 107页]。据报道，中杏仁核多巴胺能系统的特异性激活会在对引发条件性恐惧的刺激作出反应时发生[M.L.科科，C.M.库恩，T.D.伊利，C.D.基尔茨，条件性应激对中杏仁核多巴胺神经元的选择性激活：地西泮的减弱作用。《脑研究》590（1992年）39 - 47页]，这表明杏仁核中的多巴胺释放可能有助于条件性恐惧的习得和/或表达。实验1A采用2×2析因设计，研究了双侧杏仁核内注射选择性D1受体拮抗剂SCH 23390（2.0微克/0.5微升/侧）对通过对声音和背景情境刺激的僵住反应来测量的巴甫洛夫条件性恐惧的习得和表达的影响。在习得训练前、留存测试前或两者之前注射SCH 23390，均显著减弱了留存测试期间的条件性僵住反应。实验1B研究了训练前注射不同剂量（0.5、1.0和2.0微克）的SCH 23390对条件性恐惧的剂量依赖性影响。训练前注射SCH 23390在留存测试期间剂量依赖性地减弱了条件性僵住反应。实验2A研究了双侧注射选择性D1受体激动剂SKF 82958（2.0微克/0.5微升/侧）对条件性恐惧的习得和表达的影响。训练前注射SKF 82958促进了留存测试期间的条件性僵住反应。实验2B研究了训练前注射不同剂量（1.0、2.0和4.0微克）的SKF 82958对条件性恐惧的剂量依赖性影响。训练前注射SKF 82958在留存测试期间剂量依赖性地促进了条件性僵住反应。总之，这些结果表明杏仁核内的多巴胺传递有助于巴甫洛夫恐惧条件反射的习得和表达。
