Gould Thomas J, Lewis Michael C
Temple University, Psychology Department/Neuroscience Program, Philadelphia, PA 19122, USA.
Learn Mem. 2005 Jul-Aug;12(4):389-98. doi: 10.1101/lm.89105.
The present study investigated the hypothesis that both nicotinic acetylcholinergic receptors (nAChRs) and glutamate receptors (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) and N-methyl-d-aspartate glutamate receptors (NMDARs)) are involved in fear conditioning, and may modulate similar processes. The effects of the nAChR antagonist mecamylamine administered alone, the AMPAR antagonist NBQX administered alone, and the NMDAR antagonist MK-801 administered alone on cued fear conditioning, contextual fear conditioning, and latent inhibition of cued fear conditioning were examined. In addition, the effects of coadministration of either mecamylamine and NBQX or mecamylamine and MK-801 on these behaviors were examined. Consistent with previous studies, neither mecamylamine nor NBQX administered alone disrupted any of the tasks. However, coadministration of mecamylamine and NBQX disrupted both contextual fear conditioning and latent inhibition of cued fear conditioning. In addition, coadministration of mecamylamine with a dose of MK-801 subthreshold for disrupting either task disrupted both contextual fear conditioning and latent inhibition of cued fear conditioning. Coadministration of mecamylamine and NBQX, and coadministration of mecamylamine with a dose of MK-801 subthreshold for disrupting fear conditioning had little effect on cued fear conditioning. These results suggest that nAChRs and glutamate receptors may support similar processes mediating acquisition of contextual fear conditioning and latent inhibition of fear conditioning.
烟碱型乙酰胆碱能受体（nAChRs）和谷氨酸受体（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPARs）以及N-甲基-D-天冬氨酸谷氨酸受体（NMDARs））均参与恐惧条件反射，并可能调节相似的过程。研究了单独给予nAChR拮抗剂美加明、单独给予AMPAR拮抗剂NBQX以及单独给予NMDAR拮抗剂MK-801对线索性恐惧条件反射、情境性恐惧条件反射和线索性恐惧条件反射的潜伏抑制的影响。此外，还研究了美加明与NBQX或美加明与MK-801联合给药对这些行为的影响。与先前的研究一致，单独给予美加明或NBQX均未破坏任何一项任务。然而，美加明与NBQX联合给药破坏了情境性恐惧条件反射和线索性恐惧条件反射的潜伏抑制。此外，美加明与低于破坏任一任务阈值剂量的MK-801联合给药破坏了情境性恐惧条件反射和线索性恐惧条件反射的潜伏抑制。美加明与NBQX联合给药以及美加明与低于破坏恐惧条件反射阈值剂量的MK-801联合给药对线索性恐惧条件反射影响不大。这些结果表明，nAChRs和谷氨酸受体可能支持介导情境性恐惧条件反射的获得和恐惧条件反射的潜伏抑制的相似过程。
