Gong L, Kostrzewa R M, Brus R, Fuller R W, Perry K W
Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City 37614.
Brain Res Dev Brain Res. 1993 Nov 19;76(1):59-65. doi: 10.1016/0165-3806(93)90122-q.
Neonatal 6-hydroxydopamine (6-OHDA) treatment of rats is associated with supersensitization of the dopamine (DA) D1 agonist induction of stereotyped and locomotor behaviors. The present study was conducted to determine whether ontogenetic treatments of these rats with the DA D1 receptor agonist, SKF 38393, would produce a maximal DA D1 receptor supersensitivity, as measured by locomotor behavior in adulthood. Rat pups were treated daily with SKF 38393-HCl (3.0 mg/kg per day, i.p.) or saline vehicle for 28 consecutive days from birth. These animals were additionally treated at 3 days after birth with 6-OHDA-HBr (100 micrograms, in each lateral ventricle, salt form) or its vehicle. Between 6 and 9 weeks locomotor activity or stereotyped behaviors were observed after weekly challenge doses of SKF 38393-HCl (3.0 mg/kg, i.p.). In the neonatal 6-OHDA group, successive SKF 38393 treatments produced progressively greater locomotor activity. In the group of rats treated during postnatal ontogeny with both 6-OHDA and SKF 38393 daily treatments, the first adult challenge dose of SKF 38393 produced an enhanced locomotor response, greater than that seen in other groups (P < 0.01). Subsequent SKF 38393 treatments of this group produced increasingly greater locomotor responses. SKF 38393-induced stereotyped behavioral effects were greater in the 6-OHDA-lesioned groups, whether or not SKF 38393 was administered ontogenetically. Profound reductions (> 99%) of DA and its metabolites were found in the striatum of neonatal 6-OHDA treated rats, regardless of whether SKF 38393 was co-administered ontogenetically.(ABSTRACT TRUNCATED AT 250 WORDS)
用6 - 羟基多巴胺（6 - OHDA）处理新生大鼠会使多巴胺（DA）D1激动剂诱导的刻板行为和运动行为出现超敏反应。本研究旨在确定用DA D1受体激动剂SKF 38393对这些大鼠进行个体发育处理，是否会如通过成年期运动行为所测的那样，产生最大程度的DA D1受体超敏反应。从出生起，给幼鼠连续28天每日腹腔注射SKF 38393 - HCl（3.0毫克/千克/天）或生理盐水。这些动物在出生后3天还额外接受了6 - OHDA - HBr（100微克，于每个侧脑室，盐形式）或其溶剂处理。在6至9周龄时，每周腹腔注射一次SKF 38393 - HCl（3.0毫克/千克）作为激发剂量后，观察其运动活动或刻板行为。在新生6 - OHDA组中，连续的SKF 38393处理使运动活动逐渐增强。在出生后个体发育期间同时接受6 - OHDA和SKF 38393每日处理的大鼠组中，首次成年期激发剂量的SKF 38393产生了增强的运动反应，大于其他组所见（P < 0.01）。该组随后的SKF 38393处理产生了越来越大的运动反应。无论SKF 38393是否在个体发育期间给药，SKF 38393诱导的刻板行为效应在6 - OHDA损伤组中都更大。在新生6 - OHDA处理的大鼠纹状体中发现多巴胺及其代谢产物显著减少（> 99%），无论SKF 38393是否在个体发育期间共同给药。（摘要截选至250字）
