CLIMBING BEHAVIOR INDUCED BY APOMORPHINE IN MICE - POTENTIAL MODEL FOR DETECTION OF NEUROLEPTIC ACTIVITY
CLIMBING BEHAVIOR INDUCED BY APOMORPHINE IN MICE - POTENTIAL MODEL FOR DETECTION OF NEUROLEPTIC ACTIVITY
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DOI：
10.1016/0014-2999(78)90251-0
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发表时间：
1978-01-01
影响因子：
5
通讯作者：
NOHRIA, V
中科院分区：
文献类型：
--
作者：
COSTALL, B;NAYLOR, RJ;NOHRIA, V
阿波啡和假定的多巴胺激动剂2-（N，N-二丙基）-氨基-5,6-二羟四乙胺诱导小鼠的剂量依赖性攀爬行为，在铁丝网笼中测量第一次攀爬后30分钟内攀爬时间的百分比，以及在药物作用期间单次攀爬所花费的最大时间。这两种措施通常是平行的，除非相互作用的药物引起肌肉张力低下。以所有可能相互作用的药物为前处理，观察1.0 mg/kg阿波啡对攀爬大鼠运动功能的影响。还考虑了阿波啡对刻板咬伤的反应发生变化的可能性，这也会干扰攀爬。排除这些非特异性变化，爬升行为被证明是剂量依赖性的，被低剂量的典型和非典型抗精神病药物（氟哌啶醇、氟非那嗪、洛沙平、吡莫啶、奥培胺、氯氮平、硫氮嗪、舒必利、硫必利和甲氧氯普胺）拮抗，但不被其他精神活性药物特异性拮抗。5 -羟色胺能药物能改变攀爬行为；激动剂喹帕嗪减少或消除，而拮抗剂甲塞吉胺和赛庚啶增强反应。微腐毒素特异性地减少攀爬行为，但戊酸钠发挥非特异性作用，排除了GABA参与的结论。攀爬时胆碱能和去甲肾上腺素能的影响也明显被阿托品、乙酰哌啶酮、哌洛酮和心得安的无效所消除。5 -羟色胺与攀爬的关系扩展到抗精神病药物的作用：典型的抗精神病药物（氟哌啶醇、氟非那嗪、氯沙平）与甲塞吉特或赛庚啶联合使用时，其拮抗作用显著增强，而氯氮平、硫吡嗪和噻嗪的作用则显著降低。甲氯普胺、奥培胺、匹莫齐特和噻必利的作用一般不会因这种联合而改变。根据诱导锥体外系紊乱的不同能力讨论了这些差异，并将小鼠攀爬模型作为一种具有检测不同活性谱的抗精神病药物潜力的测试。
Apomorphine and the putative dopamine agonist, 2-(N,N-dipropyl)-amino-5,6-dihydroxytetralin induced dose-dependent climbing behaviour in the mouse which was measured in wire mesh lined cages as the percentage of time spent climbing in the 30 min period following the first climb and as the maximum time spent in a single climb throughout the drug effect. These two measures were generally found to parallel excepting when the interacting agent caused muscular hypotonia. All potential interacting agents were given as pretreatments to determine changes in motor function which may interfere with the climbing induced by 1.0 mg/kg s.c. apomorphine. The possibility of a change in the apomorphine response to a stereotyped biting, which would also interfere with climbing, was also considered. Excluding these non-specific changes, climbing behaviour was shown to be antagonised, dose-dependently, by low doses of typical and atypical neuroleptic agents (haloperidol, fluphenazine, loxapine, pimodize, oxiperomide, clozapine, thioridazine, sulpiride, tiapride and metoclopramide) but not specifically by other psychoactive agents. Climbing behaviour was modified by serotonergic agents; the agonist quipazine reduced or abolished, whilst the antagonist, methysergide and cyproheptadine, enhanced the response. Picrotoxin specifically reduced climbing behaviour but sodium valporate exerted non-specific effects, precluding conclusions as to a GABA involvement. Cholinergic and noradrenergic involvements with climbing were also apparently eliminated by the ineffectiveness of atropine, aceperone, piperoxan and propranolol. The involvement of serotonin with climbing was extended to the actions of the neuroleptics: the antagonistic effects of typical neuroletpics (haloperidol, fluphenazine, loxapine) were markedly enhanced by combination with methysergide or cyproheptadine whilst the effects of clozapine, sulpiride and thioridazine were significantly reduced. The actions of methoclopramide, oxiperomide, pimozide and tiapride were not generally modifed by such combinations. These differences are discussed in terms of differential abilities to induce extrapyramidal disturbances and the mouse climbing model is forwarded as a test with potential to detect antipsychotic agents of different activity spectra.