Elphick M, Anderson S M, Hallis K F, Grahame-Smith D G
MRC Unit, Radcliffe Infirmary, Oxford, UK.
Psychopharmacology (Berl). 1990;100(1):49-53. doi: 10.1007/BF02245789.
The effects of carbamazepine (CBZ) on brain 5-hydroxytryptamine (5-HT) function were investigated in rodents pretreated with CBZ acutely or for 14 days. In behavioural experiments, mice pretreated with 14 days CBZ showed increased 5-HT2-mediated head twitch behaviour after injection of carbidopa (25 mg/kg) followed by 5-hydroxytryptophan (5-HTP, 100 mg/kg). However, no change in head twitches after 5-methoxy,N,N,-dimethyltryptamine (5MeODMT 5.0 mg/kg), a direct agonist, was observed. Chronic CBZ administration to rats did not alter either the behavioural syndrome induced by 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT, 1.0 mg/kg), an index of postsynaptic 5-HT1A responses, or hypothermia after 8-OH-DPAT (0.5 mg/kg) which is thought to reflect presynaptic 5-HT1A activity. Both hyperactivity and the behavioural syndrome seen after tranylcypromine (20 mg/kg) followed by L-tryptophan (100 mg/kg) were decreased by prior treatment with CBZ (14 days). Accumulation of 5-HTP after administration of the amino acid decarboxylase inhibitor NSD1015 (100 mg/kg) was decreased after acute CBZ (50 mg/kg) in hippocampus. However, after 14 days oral treatment no change in this measure of 5-HT synthesis was seen, in either hippocampus or frontal cortex. CBZ (50 microM) added to superfused brain slices did not affect potassium-stimulated [3H]-5-HT release. However, hippocampal slices from rats pretreated with CBZ (14 days) showed increased potassium-stimulated [3H]-5-HT release. CBZ (14 days) did not alter 5-HT2 binding in rat frontal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了卡马西平（CBZ）对急性或连续14天接受CBZ预处理的啮齿动物脑5-羟色胺（5-HT）功能的影响。在行为实验中，连续14天接受CBZ预处理的小鼠在注射卡比多巴（25 mg/kg）后再注射5-羟色氨酸（5-HTP，100 mg/kg），5-HT2介导的头部抽搐行为增加。然而，直接激动剂5-甲氧基-N，N-二甲基色胺（5MeODMT 5.0 mg/kg）注射后，未观察到头部抽搐有变化。对大鼠长期给予CBZ，既未改变由8-羟基-2-二丙基氨基四氢萘（8-OH-DPAT，1.0 mg/kg）诱导的行为综合征（突触后5-HT1A反应指标），也未改变8-OH-DPAT（0.5 mg/kg）后的体温过低情况（这被认为反映突触前5-HT1A活性）。事先用CBZ（14天）处理可降低反苯环丙胺（20 mg/kg）后再给予L-色氨酸（100 mg/kg）所出现的多动和行为综合征。给予氨基酸脱羧酶抑制剂NSD1015（100 mg/kg）后，急性给予CBZ（50 mg/kg）可使海马中5-HTP的蓄积减少。然而，口服14天后，在海马或额叶皮质中，这种5-HT合成指标均未发生变化。添加到脑片灌流液中的CBZ（50 μM）不影响钾刺激的[3H]-5-HT释放。然而，经CBZ（14天）预处理的大鼠海马脑片显示钾刺激的[3H]-5-HT释放增加。CBZ（14天）未改变大鼠额叶皮质中的5-HT2结合。（摘要截短于250字）
