Schrott L M, Getty M E, Wacnik P W, Sparber S B
Department of Pharmacology, University of Minnesota Medical School, Minneapolis 55455, USA.
Pharmacol Biochem Behav. 1998 Sep;61(1):9-17. doi: 10.1016/s0091-3057(98)00013-6.
Exposure to drugs of abuse during embryogenesis may adversely affect nervous, immune, and endocrine systems development. We compared exposure on embryonic day 18 (E18) by single or multiple cocaine (COC) injections (56.25 mg/kg total dose for both) or saline on hatching and activity measures. In saline-exposed controls, repeated testing, age, and gender affected activity levels. A single or multiple COC injections increased the median latency to explore and multiple COC injections decreased the median number of lines crossed by female chicks in the open field. We also determined if pretreatment with the serotonin2 (5-HT2) receptor antagonist ritanserin could attenuate COC's effects on open-field behavior as well as behaviors sensitive to immune system stimulation (lipopolysaccharide (LPS)-induced sickness behavior). Eggs containing embryos were pretreated on E17 with 0.4 mg ritanserin/kg or its vehicle followed by multiple COC injections or saline on E18. E18 COC treatment decreased the median number of lines crossed and distress vocalizations in females. Ritanserin pretreatment mitigated the COC induced effects. E18 COC exposure also suppressed LPS-induced sickness behaviors in both males and females, increasing food consumption and the time spent awake and active, as well as decreasing the time spent sleeping. Ritanserin alone had no effect on the food consumed or time spent active, nor did this dose affect COC-induced alterations in sickness behavior. Ritanserin alone decreased time spent sleeping and also failed to affect the COC-induced suppression. Thus, embryonic COC exposure can suppress open field and LPS-induced sickness behavior in the young chick, and ritanserin pretreatment can block the former, but not the latter effects at the dose chosen for these experiments.
胚胎发育期间接触滥用药物可能会对神经、免疫和内分泌系统的发育产生不利影响。我们比较了在胚胎第18天（E18）通过单次或多次注射可卡因（COC）（两种方式的总剂量均为56.25 mg/kg）或生理盐水对孵化和活动指标的影响。在生理盐水处理的对照组中，重复测试、年龄和性别会影响活动水平。单次或多次注射COC会增加探索的中位潜伏期，多次注射COC会减少雌性雏鸡在旷场中穿越的中线数量。我们还确定了用5-羟色胺2（5-HT2）受体拮抗剂利坦色林预处理是否可以减弱COC对旷场行为以及对免疫系统刺激敏感的行为（脂多糖（LPS）诱导的疾病行为）的影响。在E17时，用0.4 mg/kg利坦色林或其溶媒对含有胚胎的鸡蛋进行预处理，然后在E18时进行多次COC注射或生理盐水处理。E18时COC处理减少了雌性穿越的中线数量和痛苦叫声。利坦色林预处理减轻了COC诱导的影响。E18时接触COC还抑制了雄性和雌性LPS诱导的疾病行为，增加了食物消耗以及清醒和活动的时间，同时减少了睡眠时间。单独使用利坦色林对食物消耗或活动时间没有影响，该剂量也未影响COC诱导的疾病行为改变。单独使用利坦色林减少了睡眠时间，也未能影响COC诱导的抑制作用。因此，胚胎期接触COC可抑制幼雏的旷场和LPS诱导的疾病行为，利坦色林预处理可阻断前者，但在这些实验所选用的剂量下不能阻断后者的作用。
