Paroxetine is effective in desensitizing 5-HT1A receptor function in adult offspring exposed prenatally to cocaine.
Paroxetine is effective in desensitizing 5-HT1A receptor function in adult offspring exposed prenatally to cocaine.
复制标题
帕罗西汀可有效使产前接触可卡因的成年后代的 5-HT1A 受体功能脱敏。
DOI：
10.1007/s00213-005-2249-8
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发表时间：
2005
影响因子：
3.4
通讯作者：
Battaglia,George
中科院分区：
文献类型：
--
作者：
Chen,Zhuo;Tetzlaff,Julie;Sripathirathan,Kumar;Carrasco,GonzaloA;Shankaran,Mahalakshmi;VanDeKar,LouisD;Muma,NancyA;Battaglia,George
RationaleDesensitization of postsynaptic 5-HT1Areceptors may be responsible for the therapeutic effectiveness of serotonin selective uptake inhibitors (SSRIs). As prenatal cocaine exposure produces long-term deficits in 5-HT neurons in offspring, it may alter the ability of postsynaptic 5-HT1Areceptors to be desensitized by chronic paroxetine.ObjectivesThe aim of the study is to determine (1) prenatal cocaine-induced changes in 5-HT1Areceptor function and (2) the effectiveness of chronic treatment with paroxetine to produce 5-HT1Areceptor desensitization in adult offspring exposed to cocaine in utero.MethodsPregnant rats received saline or (−)cocaine (15 mg/kg, s.c.) twice daily from gestational days 13 through 20. Adult male offspring from each of prenatal groups were treated with saline or paroxetine (10 mg/kg/day; i.p.) for 14 days. Eighteen hours post-treatment, rats were challenged with saline or the 5-HT1Areceptor agonist (+)8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.04 or 0.2 mg/kg, s.c.). Plasma oxytocin, adrenocorticotropic hormone (ACTH), corticosterone, renin and prolactin were determined.ResultsPrenatal cocaine exposure did not alter 5-HT1Areceptor-mediated neuroendocrine responses. Paroxetine treatment desensitized 5-HT1Areceptor-mediated increases in oxytocin, ACTH and corticosterone to a comparable extent in all offspring and reduced theEmaxfor ACTH only in prenatal cocaine-exposed offspring. Cortical [3H]-8-OH-DPAT- or [3H]-WAY100635-labeled 5-HT1Areceptors were unaltered by prenatal cocaine or subsequent paroxetine treatment.ConclusionsPostsynaptic 5-HT1Areceptor function is unaltered by prenatal cocaine exposure and paroxetine can effectively desensitize 5-HT1Areceptor function in adult cocaine-exposed offspring. These data suggest that paroxetine may be clinically effective in treating mood disorders in adults exposed in utero to cocaine.
