Grahn R E, Watkins L R, Maier S F
Department of Psychology, Connecticut College, Box 5275, 270 Mohegan Avenue, 06320-4196, New London, CT 06320-4196, USA.
Behav Brain Res. 2000 Jul;112(1-2):33-41. doi: 10.1016/s0166-4328(00)00161-3.
Exposure to uncontrollable aversive events produces a variety of behavioral consequences that do not occur if the aversive event is controllable. Accumulating evidence suggests that exaggerated excitation of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) is sufficient to cause these same behaviors, such as poor shuttlebox escape performance and enhanced conditioned fear that occur 24 h after exposure to inescapable tailshock (IS). The aim of the present studies was to explore the possibility that N-methyl-D-aspartate (NMDA) receptor activation and nitric oxide (NO) formation within the DRN might be involved in mediating the behavioral consequences of IS. To this end, either the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV) or the nitric oxide synthase inhibitor Nw-nitro-L-arginine methyl ester (L-NAME), was microinjected into the DRN before IS or before testing 24 h later. Blocking NMDA receptors with APV in the DRN during IS prevented the usual impact of IS on escape responding and conditioned fear. However, injection of APV at the time of testing only reduced these effects. The DRN was shown to be the critical site mediating blockade of these behavioral changes since injection of APV lateral to the DRN did not alter the behavioral consequences of IS. Conversely, L-NAME was most effective in reversing the effects of IS when administered at the time of testing. These results suggest that there is glutamatergic input to the DRN at the time of IS that produces long-lasting changes in DRN sensitivity. This plasticity in the DRN is discussed as a possible mechanism by which IS leads to changes in escape performance and conditioned fear responding.
暴露于不可控的厌恶事件会产生多种行为后果，而如果厌恶事件是可控的，则不会出现这些后果。越来越多的证据表明，中缝背核（DRN）中血清素（5-HT）神经元的过度兴奋足以导致这些相同的行为，例如在暴露于不可逃避的尾部电击（IS）24小时后出现的穿梭箱逃避表现不佳和条件性恐惧增强。本研究的目的是探讨DRN内N-甲基-D-天冬氨酸（NMDA）受体激活和一氧化氮（NO）形成可能参与介导IS行为后果的可能性。为此，在IS之前或24小时后的测试之前，将NMDA受体拮抗剂2-氨基-5-磷酸缬氨酸（APV）或一氧化氮合酶抑制剂Nw-硝基-L-精氨酸甲酯（L-NAME）微量注射到DRN中。在IS期间用APV阻断DRN中的NMDA受体会阻止IS对逃避反应和条件性恐惧的通常影响。然而，在测试时注射APV只会降低这些影响。由于在DRN外侧注射APV不会改变IS的行为后果，因此DRN被证明是介导这些行为变化阻断的关键部位。相反，L-NAME在测试时给药最有效地逆转了IS的影响。这些结果表明，在IS时存在谷氨酸能输入到DRN，从而在DRN敏感性上产生持久变化。DRN中的这种可塑性被讨论为IS导致逃避表现和条件性恐惧反应变化的一种可能机制。
