Gray J A, Moran P M, Grigoryan G, Peters S L, Young A M, Joseph M H
Department of Psychology, Institute of Psychiatry, London, UK.
Behav Brain Res. 1997 Oct;88(1):27-34. doi: 10.1016/s0166-4328(97)02313-9.
It has been proposed that dopaminergic transmission in the nucleus accumbens plays a key role in regulating latent inhibition (LI), i.e. the retardation of conditioning that occurs if a to-be-conditioned stimulus is first presented a number of times ('preexposure') without other consequence. New evidence in support of this hypothesis is presented or reviewed here, showing that: (1) intra-accumbens injection of haloperidol at the time of conditioning potentiates LI; (2) destruction of dopaminergic terminals in the nucleus accumbens potentiates LI; (3) intra-accumbens haloperidol reverses the blockade of LI caused by systemic nicotine; (4) intra-accumbens haloperidol reverses the blockade of LI caused by systemic amphetamine; (5) after a single systemic injection of amphetamine (insufficient on its own to block LI), a subsequent intra-accumbens injection of amphetamine at the time of conditioning blocks LI; and (6) intra-accumbens (like systemic) amphetamine administered 15 min before conditioning, without prior systemic amphetamine, failed to block LI. The difference between the effects on LI of one and two administrations of amphetamine, respectively, is interpreted in terms of the need for sensitisation of the response to amphetamine, with the result that the response to the second administration includes a component of impulse-dependent dopamine release in the nucleus accumbens that is otherwise lacking. Data from dialysis experiments suggest that such impulse-dependent accumbens dopamine release also occurs at relatively long delays after a single systemic administration of amphetamine. It was accordingly predicted, and found, that, although LI is intact 15 min after an i.p. injection (confirming previous results), it is abolished at 90 min after the injection of amphetamine. This finding is consistent with the effects of amphetamine in human subjects, in whom LI is blocked 90 min after a single oral administration. Overall, these results strengthen the case that the blockade of LI by elevated, and potentiation of LI by decreased, dopaminergic transmission are both due specifically to actions in the nucleus accumbens; and also add to the similarities between LI studied in animal and human subjects, respectively.
有人提出，伏隔核中的多巴胺能传递在调节潜伏抑制（LI）中起关键作用，即如果一个待条件刺激首先多次呈现（“预暴露”）而无其他后果，那么条件作用就会延迟。本文展示或回顾了支持这一假说的新证据，表明：（1）在条件作用时向伏隔核内注射氟哌啶醇可增强潜伏抑制；（2）破坏伏隔核中的多巴胺能终末可增强潜伏抑制；（3）向伏隔核内注射氟哌啶醇可逆转全身给予尼古丁对潜伏抑制的阻断作用；（4）向伏隔核内注射氟哌啶醇可逆转全身给予苯丙胺对潜伏抑制的阻断作用；（5）在单次全身注射苯丙胺（单独不足以阻断潜伏抑制）后，随后在条件作用时向伏隔核内注射苯丙胺可阻断潜伏抑制；（6）在条件作用前15分钟向伏隔核内（与全身给药类似）注射苯丙胺，且之前未进行全身苯丙胺给药，未能阻断潜伏抑制。分别给予一次和两次苯丙胺对潜伏抑制的影响差异，根据对苯丙胺反应的敏化需求来解释，结果是对第二次给药的反应包括伏隔核中冲动依赖性多巴胺释放这一原本不存在的成分。透析实验数据表明，在单次全身注射苯丙胺后较长时间延迟时，也会发生这种冲动依赖性伏隔核多巴胺释放。因此可以预测并发现，虽然腹腔注射后15分钟潜伏抑制完好（证实了先前的结果），但在注射苯丙胺后90分钟潜伏抑制被消除。这一发现与苯丙胺对人类受试者的影响一致，在人类中，单次口服苯丙胺90分钟后潜伏抑制被阻断。总体而言，这些结果进一步证明，多巴胺能传递增强对潜伏抑制的阻断以及多巴胺能传递减少对潜伏抑制的增强，均具体归因于伏隔核中的作用；同时也增加了分别在动物和人类受试者中研究的潜伏抑制之间的相似性。
