Stewart B R, Jenner P, Marsden C D
University Department of Neurology, King's College Hospital Medical School, London, UK.
Psychopharmacology (Berl). 1988;96(1):55-62. doi: 10.1007/BF02431533.
Purposeless chewing in rats was induced by the acute administration of the cholinergic agonist pilocarpine or by physostigmine. Pilocarpine-induced chewing was antagonised by the centrally acting anticholinergic drugs scopolamine, benzhexol and secoverine, but not by the peripherally acting anticholinergic drug methylscopolamine. Both benzhexol and secoverine caused dose-dependent inhibition of pilocarpine-induced chewing. The D-2 antagonist sulpiride and the D-1 antagonist SCH 23390 did not inhibit pilocarpine-induced chewing. The non-selective neuroleptics pimozide, trifluoperazine and thioridazine also were inactive. In contrast, clozapine caused a dose-related inhibition of pilocarpine-induced chewing. The alpha-1 antagonist prazosin, the alpha-2 antagonist idazoxan, the beta-antagonists propranolol and metoprolol and the H-1 antagonist mepyramine did not reduce pilocarpine-induced chewing. Purposeless chewing behaviour induced by pilocarpine was reduced in a dose-related manner by the administration of the 5-HT antagonists methiothepin and mianserin, but not by spiperone or ketanserin. These data confirm that pilocarpine-induced chewing behaviour in the rat is a model of central cholinergic activity, but suggest that a serotonergic component may be involved in the mediation of this behaviour.
通过急性给予胆碱能激动剂毛果芸香碱或毒扁豆碱可诱导大鼠出现无目的咀嚼。毛果芸香碱诱导的咀嚼可被中枢作用的抗胆碱能药物东莨菪碱、苯海索和西沃明拮抗,但不能被外周作用的抗胆碱能药物甲基东莨菪碱拮抗。苯海索和西沃明均引起毛果芸香碱诱导咀嚼的剂量依赖性抑制。D-2拮抗剂舒必利和D-1拮抗剂SCH 23390不抑制毛果芸香碱诱导的咀嚼。非选择性抗精神病药物匹莫齐特、三氟拉嗪和硫利达嗪也无活性。相比之下,氯氮平引起毛果芸香碱诱导咀嚼的剂量相关性抑制。α-1拮抗剂哌唑嗪、α-2拮抗剂伊达唑新、β-拮抗剂普萘洛尔和美托洛尔以及H-1拮抗剂美吡拉敏均未减少毛果芸香碱诱导的咀嚼。给予5-HT拮抗剂甲硫噻平及米安色林后,毛果芸香碱诱导的无目的咀嚼行为呈剂量相关性减少,但螺哌隆或酮色林则无此作用。这些数据证实,大鼠中毛果芸香碱诱导的咀嚼行为是中枢胆碱能活性的一种模型,但提示5-羟色胺能成分可能参与了该行为的介导。