Chen Zhuo, Waimey Kate, Van de Kar Louis D, Carrasco Gonzalo A, Landry Michelle, Battaglia George
Department of Pharmacology and Center for Serotonin Disorders Research, Loyola University of Chicago, Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA.
Neuropharmacology. 2004 Jun;46(7):942-53. doi: 10.1016/j.neuropharm.2004.01.013.
This study investigated the ability of prenatal exposure to cocaine to alter serotonin(2A) (5-HT(2A)) receptor function and paroxetine-induced desensitization of 5-HT(2A) receptor function in rat offspring. Following exposure to saline or (-)cocaine (15 mg/kg, s.c., b.i.d.), during gestational days 13-20, adult male offspring were treated with either saline or paroxetine (10 mg/kg/day, i.p. 14 days). Eighteen hours post-treatment, changes in the stimulation of oxytocin, adrenocorticotropic hormone (ACTH) and corticosterone by (-)4-iodo-2,5-dimethoxyphenylisopropylamine (DOI, 0.5 or 2.0 mg/kg, s.c.) and in 5-HT(2A) receptor densities were determined. Prenatal cocaine exposure did not alter 5-HT(2A) receptor-mediated neuroendocrine responses or 5-HT(2A) receptor densities. In contrast, paroxetine treatment reduced cortical 5-HT(2A) receptors (18-25%) and desensitized 5-HT(2A) receptor-mediated oxytocin responses in both offspring groups. Furthermore, in cocaine offspring, paroxetine produced an inhibition of 5-HT(2A) receptor-mediated increase in plasma ACTH levels and a greater attenuation of the oxytocin responses to (-)DOI. Paroxetine-induced reductions in body weight gain (-8.8%) were comparable in both offspring groups. These data, demonstrating that prenatal exposure to cocaine potentiates paroxetine-induced desensitization of 5-HT(2A) receptor function, may be clinically relevant with respect to treating mood disorders in adults exposed in utero to cocaine.
本研究调查了产前接触可卡因对大鼠后代5-羟色胺（2A）（5-HT（2A））受体功能以及帕罗西汀诱导的5-HT（2A）受体功能脱敏的影响。在妊娠第13至20天，成年雄性后代在接触生理盐水或（-）可卡因（15mg/kg，皮下注射，每日两次）后，接受生理盐水或帕罗西汀（10mg/kg/天，腹腔注射，共14天）治疗。治疗后18小时，测定（-）4-碘-2,5-二甲氧基苯异丙胺（DOI，0.5或2.0mg/kg，皮下注射）对催产素、促肾上腺皮质激素（ACTH）和皮质酮的刺激变化以及5-HT（2A）受体密度。产前接触可卡因未改变5-HT（2A）受体介导的神经内分泌反应或5-HT（2A）受体密度。相比之下，帕罗西汀治疗使两个后代组的皮质5-HT（2A）受体减少（18 - 25%），并使5-HT（2A）受体介导的催产素反应脱敏。此外，在可卡因暴露的后代中，帕罗西汀抑制了5-HT（2A）受体介导的血浆ACTH水平升高，并对催产素对（-）DOI的反应产生更大程度的减弱。帕罗西汀引起的体重增加减少（-8.8%）在两个后代组中相当。这些数据表明，产前接触可卡因增强了帕罗西汀诱导的5-HT（2A）受体功能脱敏，这对于治疗子宫内接触可卡因的成年人的情绪障碍可能具有临床意义。
