Henderson M G, McConnaughey M M, McMillen B A
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858.
Brain Res Bull. 1991 Jun;26(6):941-5. doi: 10.1016/0361-9230(91)90261-h.
Reports from both this laboratory and others indicate that prenatal exposure of rats to cocaine can produce alterations in development, activity and responses to environmental stimuli. In order to determine a biochemical basis for these effects, radioligand receptor-binding assays for different monoaminergic receptors were performed on rat brain tissues obtained from offspring of dams treated SC with saline, cocaine (15 mg/kg b.i.d.), amitriptyline (10 mg/kg) or amfonelic acid (AFA, 1.5 mg/kg). Male rat pups were fostered by surrogate dams and one rat per litter taken at 30, 60 or 180 days postnatal for determination of striatal and prefrontal cortical D2 receptors, prefrontal cortical 5HT2 receptors, cortical alpha 1-, alpha 2-, beta 1- and beta 2-adrenoceptors. Across all drug treatments and times, the only significant change was at 30 days of age when beta 1-adrenoceptors were increased 68% in the cocaine exposed pups--a time when these rats show hyperactivity--and at 180 days postnatal when a 20% decrease in DA2 receptor Bmax was observed. Also, cortical membrane Mg(2+)-dependent Na+, K(+)-ATPase activities and basal ATPase activities were unaltered by any of the treatments at any of the times. These results suggest that few changes have occurred in monoaminergic receptor sensitivity as a result of the exposure to these drugs during gestation. The behavioral changes that are known to occur following prenatal exposure to cocaine may be due to presynaptic alterations in neurotransmitter function rather than changes in postsynaptic receptors.
本实验室及其他机构的报告表明，大鼠孕期接触可卡因可导致发育、活动及对环境刺激的反应发生改变。为确定这些效应的生化基础，对经皮下注射生理盐水、可卡因（15毫克/千克，每日两次）、阿米替林（10毫克/千克）或氨苯酸（AFA，1.5毫克/千克）处理的母鼠所产子代大鼠的脑组织进行了不同单胺能受体的放射性配体结合测定。雄性幼鼠由代孕母鼠抚养，每窝选取一只在出生后30、60或180天处死，用于测定纹状体和前额叶皮质的D2受体、前额叶皮质的5HT2受体、皮质α1 -、α2 -、β1 -和β2 -肾上腺素能受体。在所有药物处理和时间点中，唯一显著的变化是在30日龄时，接触可卡因的幼鼠β1 -肾上腺素能受体增加了68%——此时这些大鼠表现出多动——以及在出生后180天，观察到DA2受体Bmax下降了20%。此外，在任何时间点，任何处理均未改变皮质膜Mg(2 +)依赖性Na +、K(+) - ATP酶活性及基础ATP酶活性。这些结果表明，孕期接触这些药物后，单胺能受体敏感性几乎没有变化。已知孕期接触可卡因后出现的行为改变可能是由于神经递质功能的突触前改变，而非突触后受体的变化。
