Hyde J F, Jerussi T P
Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ 08854.
Brain Res. 1987 Sep 22;421(1-2):117-26. doi: 10.1016/0006-8993(87)91281-9.
Following cannulation of the right common carotid artery of female Sprague-Dawley rats, 3 microCi (10 micrograms) of either [3H]haloperidol or [3H]amphetamine were infused. At various time intervals, drug concentrations were determined in the right and left striata, anterior forebrains, posterior forebrains and cerebella. One minute following unilateral intracarotid infusion of haloperidol, approximately a 90-100-fold right/left (ipsilateral/contralateral) difference in drug concentrations was attained in the striatum and the posterior forebrain, while more than a 75-fold difference was evident in the anterior forebrain. One minute following amphetamine infusion, a difference greater than 40-fold was seen in all forebrain structures. The right-left differences steadily declined with time as a result of the declining drug concentrations of the infused hemisphere. The pharmacokinetic parameters of both the distribution and elimination phases were similar in each forebrain region for both haloperidol and amphetamine. The kinetic parameters did, however, show specific drug differences. Bilateral drug concentrations in the striatum following intraperitoneal administration of amphetamine to unilaterally cannulated rats were nearly identical. Therefore, the cannulation procedure did not significantly alter the blood supply to either hemisphere. This is the first study to quantify drug concentrations and to analyze pharmacokinetic parameters following unilateral cerebral drug administration in conscious animals. This technique should be useful in studying functional and biochemical interhemispheric relationships as well as lateralized behaviors.
在对雌性Sprague-Dawley大鼠的右侧颈总动脉进行插管后，注入3微居里（10微克）的[3H]氟哌啶醇或[3H]苯丙胺。在不同的时间间隔，测定右侧和左侧纹状体、前脑、后脑和小脑的药物浓度。在单侧颈内动脉注入氟哌啶醇1分钟后，纹状体和后脑的药物浓度在右/左（同侧/对侧）之间出现了约90 - 100倍的差异，而在前脑则出现了超过75倍的差异。在注入苯丙胺1分钟后，所有前脑结构中的差异均大于40倍。由于注入半球的药物浓度下降，左右差异随时间稳步下降。氟哌啶醇和苯丙胺在每个前脑区域的分布和消除阶段的药代动力学参数相似。然而，动力学参数确实显示出特定的药物差异。对单侧插管大鼠腹腔注射苯丙胺后，纹状体中的双侧药物浓度几乎相同。因此，插管过程并未显著改变任一半球的血液供应。这是第一项在清醒动物中对单侧脑内给药后的药物浓度进行定量并分析药代动力学参数的研究。该技术在研究功能和生化半球间关系以及偏侧行为方面应具有实用性。
