Hawkins M, Pravica M, Radulovacki M
Department of Pharmacology, University of Illinois, College of Medicine, Chicago 60612.
Pharmacol Biochem Behav. 1988 Jun;30(2):303-8. doi: 10.1016/0091-3057(88)90459-5.
Following chronic administration (10 or 20 days) of diazepam (5 mg/kg/day, subcutaneous pellets) or RO 15-1788 (5 mg/kg/day, intraperitoneally), adenosine and benzodiazepine receptors in different rat brain areas were assessed by radioligand binding studies using [3H]R-PIA for A1 receptors, [3H]NECA and [3H]R-PIA for A2 receptors and [3H]FNZ for benzodiazepine receptors. Chronic administration of diazepam for 10, but not for 20 days, decreased A2 receptors in the striatum by 46% (p less than 0.05) and A1 receptors in the hippocampus by 13% (p less than 0.05). Administration of diazepam for 10 days and 20 days failed to alter [3H]FNZ binding in all brain areas studied. However, 20 days of diazepam administration decreased the magnitude of GABA enhancement of [3H]FNZ binding in the cortex by 25% (p less than 0.05). In contrast, chronic administration of RO 15-1788 failed to alter [3H]R-PIA, [3H]NECA and [3H]FNZ binding in all brain areas. These results suggest that adenosine receptors may play a role in the CNS actions of benzodiazepines.
在大鼠皮下植入含地西泮（5毫克/千克/天）或RO 15 - 1788（5毫克/千克/天，腹腔注射）的缓释丸剂进行慢性给药（10或20天）后，通过放射性配体结合研究评估不同大鼠脑区的腺苷和苯二氮䓬受体，其中使用[3H]R - PIA检测A1受体，[3H]NECA和[3H]R - PIA检测A2受体，[3H]FNZ检测苯二氮䓬受体。地西泮慢性给药10天（而非20天）可使纹状体中的A2受体减少46%（p < 0.05），海马体中的A1受体减少13%（p < 0.05）。地西泮给药10天和20天均未能改变所研究的所有脑区中[3H]FNZ的结合。然而，地西泮给药20天可使皮质中GABA增强的[3H]FNZ结合幅度降低25%（p < 0.05）。相比之下，RO 15 - 1788慢性给药未能改变所有脑区中[3H]R - PIA、[3H]NECA和[3H]FNZ的结合。这些结果表明腺苷受体可能在苯二氮䓬类药物的中枢神经系统作用中发挥作用。
