Collins P, Broekkamp C L, Jenner P, Marsden C D
Parkinson's Disease Society Experimental Research Laboratories, Biomedical Sciences Division, King's College, London, UK.
Psychopharmacology (Berl). 1991;103(4):503-12. doi: 10.1007/BF02244250.
Purposeless chewing in rats was dose dependently increased by acute administration of the dopamine D-1 receptor agonist SKF 38393 (5-20 mg/kg), the D-2 receptor antagonist sulpiride (10-100 mg/kg) and the D-2 receptor agonist quinpirole (0.05-0.25 mg/kg). Only high doses of the D-1 receptor antagonist SCH 23390 (1 and 5 mg/kg) induced purposeless chewing. SCH 23390 (0.05 mg/kg) blocked SKF 38393 (20 mg/kg)-induced purposeless chewing, but had no effect on the purposeless chewing induced by sulpiride (100 mg/kg) or quinpirole (0.1 mg/kg). A dose of SKF 38393 (5 mg/kg) which did not itself induce chewing, potentiated the increase in purposeless chewing observed after administration of sulpiride (100 mg/kg). Administration of SKF 38393 (20 mg/kg) and quinpirole (0.1 mg/kg) did not induce purposeless chewing but stereotyped licking was observed. Administration of sulpiride (100 mg/kg) with quinpirole (0.1 mg/kg) produced an incidence of purposeless chewing not different from that observed when either compound was administered alone. Acute administration of the cholinergic agonist pilocarpine (0.5-4.0 mg/kg) or the cholinesterase inhibitor physostigmine (0.05-0.2 mg/kg) increased the frequency of purposeless chewing in rats. Co-administration of pilocarpine (0.5 mg/kg) with sulpiride (100 mg/kg) increased the frequency of purposeless chewing above that seen when either compound was administered alone. Co-administration of pilocarpine (0.5 mg/kg) with SKF 38393 (20 mg/kg) increased the frequency of purposeless chewing in an additive manner. Co-administration of physostigmine (0.1 mg/kg) with sulpiride (100 mg/kg) but not SKF 38393 (20 mg/kg), increased the frequency of purposeless chewing above that observed when either compound was administered alone. Quinpirole (0.1 mg/kg)-induced purposeless chewing was not affected by co-administration with either pilocarpine (0.5 mg/kg) or physostigmine (0.1 mg/kg). The anticholinergic agent scopolamine (0.1 mg/kg) blocked the purposeless chewing induced by either SKF 38393 (20 mg/kg) or sulpiride (100 mg/kg), but had no effect on the purposeless chewing induced by quinpirole (0.1 mg/kg). Contrary to previous reports, acute manipulation of D-1 or D-2 receptor function can both enhance purposeless chewing behaviour in rats.(ABSTRACT TRUNCATED AT 400 WORDS)
急性给予多巴胺D-1受体激动剂SKF 38393(5 - 20毫克/千克)、D-2受体拮抗剂舒必利(10 - 100毫克/千克)和D-2受体激动剂喹吡罗(0.05 - 0.25毫克/千克)后,大鼠无目的咀嚼呈剂量依赖性增加。只有高剂量的D-1受体拮抗剂SCH 23390(1和5毫克/千克)会诱导无目的咀嚼。SCH 23390(0.05毫克/千克)可阻断SKF 38393(20毫克/千克)诱导的无目的咀嚼,但对舒必利(100毫克/千克)或喹吡罗(0.1毫克/千克)诱导的无目的咀嚼无影响。本身不诱导咀嚼的SKF 38393剂量(5毫克/千克),可增强给予舒必利(100毫克/千克)后观察到的无目的咀嚼增加。给予SKF 38393(20毫克/千克)和喹吡罗(0.1毫克/千克)不会诱导无目的咀嚼,但会观察到刻板舔舐。舒必利(100毫克/千克)与喹吡罗(0.1毫克/千克)联合给药产生的无目的咀嚼发生率与单独给予任一化合物时观察到的无差异。急性给予胆碱能激动剂毛果芸香碱(0.5 - 4.0毫克/千克)或胆碱酯酶抑制剂毒扁豆碱(0.05 - 0.2毫克/千克)可增加大鼠无目的咀嚼的频率。毛果芸香碱(0.5毫克/千克)与舒必利(100毫克/千克)联合给药增加的无目的咀嚼频率高于单独给予任一化合物时。毛果芸香碱(0.5毫克/千克)与SKF 38393(20毫克/千克)联合给药以相加方式增加无目的咀嚼频率。毒扁豆碱(0.1毫克/千克)与舒必利(100毫克/千克)联合给药可增加无目的咀嚼频率,高于单独给予任一化合物时,但与SKF 38393(20毫克/千克)联合给药则无此作用。喹吡罗(0.1毫克/千克)诱导的无目的咀嚼不受与毛果芸香碱(0.5毫克/千克)或毒扁豆碱(0.1毫克/千克)联合给药的影响。抗胆碱能药物东莨菪碱(0.1毫克/千克)可阻断SKF 38393(20毫克/千克)或舒必利(100毫克/千克)诱导的无目的咀嚼,但对喹吡罗(0.1毫克/千克)诱导的无目的咀嚼无影响。与先前报道相反,急性调节D-1或D-2受体功能均可增强大鼠的无目的咀嚼行为。(摘要截短至400字)