de Boer T, Bartels K, Metselaar H J, Bruinvels J
Psychopharmacology (Berl). 1980;71(3):257-67. doi: 10.1007/BF00433060.
Administration of di-n-propylacetate (DPA), an inhibitor of SSA-dehydrogenase, produces in naive rats abstinence behaviour which can be blocked by morphine and bicuculline and may be useful as a behavioural correlate of increased GABA-ergic activity. The usefulness of this model has been demonstrated by studying the effect of bicuculline, picrotoxin, strychnine, morphine, aminooxyacetic acid, 3-mercaptopropionate and thiosemicarbazide on DPA-induced abstinence behaviour. Behaviour was suppressed both by bicuculline or picrotoxin, while the selective glycine antagonist strychnine was ineffective. A comparable syndrome could not be evoked by treatment with aminooxyacetic acid, a GABA-transaminase inhibitor, indicating that the effect of DPA was not caused by inhibition of this enzyme. Instead, aminooxyacetic acid suppressed the DPA-induced abstinence behaviour, suggesting that two GABA-ergic systems with opposite effects on behaviour can be distinguished. The syndrome was also suppressed by convulsant doses of 3-mercaptopropionate, while thiosemicarbazide was ineffective. Abstinence behaviour was further suppressed by morphine with an ED50 of 0.5 mg/kg and this action could be clearly separated from its depressant effect on locomotor activity in non-treated animals. These results suggest that morphine receptors may be involved in DPA-induced abstinence behaviour. Based on these experiments a model has been proposed for GABA-ergic terminals being under the inhibitor influence of GABA-ergic autoreceptors. It is proposed that DPA-induced abstinence behaviour may be useful as a model of increased GABA-ergic activity to aid study of the regulation and properties of the GABA-ergic system in vivo.
给予二正丙基乙酸酯（DPA），一种SSA脱氢酶抑制剂，可使未接触过该药物的大鼠产生戒断行为，这种行为可被吗啡和荷包牡丹碱阻断，并且可能作为GABA能活性增加的行为相关指标。通过研究荷包牡丹碱、印防己毒素、士的宁、吗啡、氨基氧乙酸、3-巯基丙酸酯和氨基硫脲对DPA诱导的戒断行为的影响，已证明了该模型的实用性。荷包牡丹碱或印防己毒素均可抑制行为，而选择性甘氨酸拮抗剂士的宁则无效。给予氨基氧乙酸（一种GABA转氨酶抑制剂）不能诱发类似的综合征，这表明DPA的作用不是由该酶的抑制引起的。相反，氨基氧乙酸抑制了DPA诱导的戒断行为，这表明可以区分对行为有相反作用的两个GABA能系统。惊厥剂量的3-巯基丙酸酯也可抑制该综合征，而氨基硫脲则无效。吗啡以0.5mg/kg的ED50进一步抑制戒断行为，并且这种作用可与它对未处理动物运动活性的抑制作用明显区分开来。这些结果表明吗啡受体可能参与了DPA诱导的戒断行为。基于这些实验，已提出了一个模型，即GABA能终末受GABA能自身受体的抑制性影响。有人提出，DPA诱导的戒断行为可能作为GABA能活性增加的模型，有助于体内研究GABA能系统的调节和特性。
