Commissaris R L, Davis M
Neurosci Biobehav Rev. 1982 Winter;6(4):515-20. doi: 10.1016/0149-7634(82)90034-3.
The present studies examined the role of the spinal cord and the brain in mediating the effects of the hallucinogens N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) on the acoustic startle response in the rat. Systemic administration of these agents, which distributes to both the brain and spinal cord, produced opposite effects, as DMT depressed and 5-MeODMT increased acoustic startle. However, when administered directly into the lateral ventricle in the forebrain (intraventricular administration) 5-hydroxytryptamine (5-HT), DMT and 5-MeODMT all depressed acoustic startle, DMT and 5-MeODMT being about equipotent in this regard. In contrast, when administered directly into the spinal cord subarachnoid space (intrathecal administration), 5-HT and 5-MeODMT increased startle, whereas DMT was without effect. In another series of studies, the effects of systemically-administered DMT and 5-MeODMT on the "startle" elicited by electrical stimulation of the nucleus reticularis pontis caudalis (RPC) were determined. Since the RPC is the last nucleus of the primary startle circuit before the spinal cord, agents which act downstream from the RPC (i.e., in the lower brainstem and spinal cord) would be expected to alter RPC-elicited "startle," while agents which act upstream from the RPC would be without effect. Given systemically, 5-MeODMT markedly increased RPC-elicited "startle" while DMT was without effect. These data indicate that DMT and 5-MeODMT are equipotent in depressing startle through actions in the brain. In contrast, the difference in the effects of DMT and 5-MeODMT on acoustic startle is related to the spinal excitatory effects of 5-MeODMT which DMT does not possess. From the present results it is suggested that the relative potencies of DMT and 5-MeODMT in other behavioral measures may relate to the role of brain (equipotent) or spinal (5-MeODMT more potent than DMT) sites of action for the various behaviors.
本研究考察了脊髓和大脑在介导致幻剂N，N - 二甲基色胺（DMT）和5 - 甲氧基 - N，N - 二甲基色胺（5 - MeODMT）对大鼠听觉惊吓反应的影响中所起的作用。全身给予这两种药物，它们会分布到大脑和脊髓，产生相反的效果，即DMT抑制听觉惊吓，而5 - MeODMT增强听觉惊吓。然而，当直接注射到前脑侧脑室（脑室内给药）时，5 - 羟色胺（5 - HT）、DMT和5 - MeODMT均抑制听觉惊吓，在这方面DMT和5 - MeODMT的效力大致相当。相比之下，当直接注射到脊髓蛛网膜下腔（鞘内给药）时，5 - HT和5 - MeODMT增强惊吓反应，而DMT则无作用。在另一系列研究中，测定了全身给予DMT和5 - MeODMT对电刺激脑桥尾侧网状核（RPC）所引发的“惊吓”的影响。由于RPC是脊髓之前初级惊吓回路的最后一个核团，预计作用于RPC下游（即在下脑干和脊髓）的药物会改变RPC引发的“惊吓”，而作用于RPC上游的药物则无作用。全身给药时，5 - MeODMT显著增强RPC引发的“惊吓”，而DMT则无作用。这些数据表明，DMT和5 - MeODMT通过在大脑中的作用抑制惊吓的效力相当。相比之下，DMT和5 - MeODMT对听觉惊吓影响的差异与5 - MeODMT具有而DMT不具有的脊髓兴奋作用有关。从目前的结果推测，DMT和5 - MeODMT在其他行为指标中的相对效力可能与大脑（效力相当）或脊髓（5 - MeODMT比DMT效力更强）在各种行为中的作用部位有关。
