ALTERATIONS IN EXTRACELLULAR AND TISSUE-LEVELS OF BIOGENIC-AMINES IN RAT-BRAIN INDUCED BY THE SEROTONIN(2) RECEPTOR ANTAGONIST, RITANSERIN

被引:51
作者
DEVAUD, LL [1 ]
HOLLINGSWORTH, EB [1 ]
COOPER, BR [1 ]
机构
[1] WELLCOME RES LABS,DIV PHARMACOL,RES TRIANGLE PK,NC 27709
关键词
RITANSERIN; DOPAMINE; SEROTONIN; NUCLEUS ACCUMBENS; ANTIPSYCHOTIC; SCHIZOPHRENIA;
D O I
10.1111/j.1471-4159.1992.tb08461.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Systemic administration of ritanserin elicited rapid changes in dopamine (DA) and serotonin (5-HT) levels in both dialysate and neuronal tissue extracts. These effects occurred in both a site-selective and a dose-related manner. Increases in extracellular levels of DA and 5-HT in the nucleus accumbens were maximal at 120-140 min after treatment. A dose of 0.63 mg/kg of ritanserin elicited larger and more prolonged increases in extracellular DA and 5-HT levels than did the 0.3 mg/kg dose. By contrast, 0.63 mg/kg of ritanserin elicited no changes in either DA or 5-HT levels with dialysate collected from the striatum. Ritanserin also induced dose-related decreases in tissue levels of DA and 5-HT from the nucleus accumbens. The site specificity of action was again noted in that there were no dose-dependent decreases in tissue levels of DA or 5-HT measured from the striatum. Ritanserin exerted little effect on metabolite levels from either dialysate or tissue extracts. Taken together, these findings show that selective 5-HT, receptor antagonism modulates DA and 5-HT neurotransmission in a specific manner. These actions appear to involve increased release of DA and 5-HT rather than significant changes in metabolism. These findings add further weight to the importance of 5-HT2 receptor interactions as an important component of antipsychotic activity.
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页码:1459 / 1466
页数:8
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