SITES OF ACTION OF ONDANSETRON TO INHIBIT WITHDRAWAL FROM DRUGS OF ABUSE
SITES OF ACTION OF ONDANSETRON TO INHIBIT WITHDRAWAL FROM DRUGS OF ABUSE
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DOI：
10.1016/0091-3057(90)90132-2
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发表时间：
1990-05-01
影响因子：
3.6
通讯作者：
TYERS, MB
中科院分区：
文献类型：
--
作者：
COSTALL, B;JONES, BJ;TYERS, MB
选择性5-HT 3受体拮抗剂昂丹司琼的大脑作用部位，以影响行为的后果，从亚慢性治疗与地西泮，乙醇，尼古丁或可卡因的撤退进行了研究，在光/暗探索试验中的小鼠。在外周给予地西泮、乙醇、尼古丁和可卡因的亚慢性治疗期间，对试验箱光室的厌恶反应降低，但在4种治疗停药后加剧。停用地西泮（10 mg/kg IP b.i.d. 14天）、乙醇（8%/w/v饮用水，持续14天）、尼古丁（0.1 mg/kg IP b.i.d. 14天）或可卡因（1.0 mg/kg IP b.i.d.杏仁核和中缝背核注射昂丹司琼（1-10 ng）可拮抗上述作用，中缝正中核、延髓核和纹状体注射昂丹司琼（10 ng）无效。结论：杏仁核和中缝背核可能是昂丹司琼拮抗小鼠戒断4种常见药物引起的厌恶行为的作用部位，中缝背核的5-HT投射可能参与厌恶行为。
The cerebral site of action of the selective 5-HT3 receptor antagonist ondansetron to influence the behavioural consequences of withdrawal from subchronic treatment with diazepam, ethanol, nicotine or cocaine was studied in the light/dark exploration test in the mouse. The aversive response to the light compartment of the test box was reduced during a subchronic treatment with peripherally administered diazepam, ethanol, nicotine and cocaine, but was exacerbated following withdrawal from the 4 treatment. The behavioural consequences of withdrawal from diazepam (10 mg/kg IP b.i.d. 14 days), ethanol (8%/w/v drinking water for 14 days), nicotine (0.1 mg/kg IP b.i.d. 14 days) or cocaine (1.0 mg/kg IP b.i.d. 14 days) were antagonised by ondansetron injected into the amygdala and dorsal raphe nucleus (1-10 ng); injections of ondansetron (10 ng) into the median raphe nucleus, the nucleus accumbens and striatum were ineffective. It is concluded that the amygdala and dorsal raphe nucleus may be sites of action for ondamsetron to antagonise the aversive behaviour caused by withdrawal from 4 common drugs of abuse in a mouse model, and that 5-HT projections from the dorsal raphe nucleus may be involved in aversive behaviour.