Turkkan J S, Hienz R D
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21224.
Psychopharmacology (Berl). 1992;109(4):484-8. doi: 10.1007/BF02247728.
Repeated acquisition behavioral performances of normotensive and renovascular hypertensive baboons were tested before, during, and following chronic oral dosing with the beta-adrenergic antagonists atenolol HCl (2.6 mg/kg/day PO), and d,l propranolol HCl (6.8 mg/kg twice daily PO) in separate studies. Each study administered active drug for 21 consecutive days preceded and followed by 14-day baseline and recovery periods, respectively. Animals pressed five keys in sequence for food reinforcement during daily experimental sessions which consisted of alternating acquisition (new sequence learning) and performance (previously learned) task components. Atenolol increased response latencies during acquisition in comparison to performance components, and during early portions of sessions. Propranolol also increased response latencies during acquisition components in early periods of sessions, but fewer dependent measures were affected, and the magnitude of increases in response latencies was smaller (12% +/- 5 SEM) as compared with atenolol (47% +/- 13). Test doses of phencyclidine HCl (PCP) increased latencies to the same degree as atenolol. PCP markedly reduced accuracy, while atenolol or propranolol did not. Blood pressures remained stable under atenolol, and decreased by approximately 10-15 mmHg under propranolol. No differences between renovascular hypertensive and normotensive baboons were found as a function of drug conditions. Drug effects were not dependent on plasma propranolol concentration.
在单独的研究中,对正常血压和肾血管性高血压狒狒在口服β-肾上腺素能拮抗剂盐酸阿替洛尔(2.6毫克/千克/天,口服)和盐酸普萘洛尔(6.8毫克/千克,每日两次,口服)进行慢性给药之前、期间和之后的重复习得行为表现进行了测试。每项研究连续21天给予活性药物,给药前后分别有14天的基线期和恢复期。在每日实验环节中,动物按顺序按压五个按键以获取食物强化,实验环节包括交替的习得(新序列学习)和表现(先前习得)任务部分。与表现部分相比,阿替洛尔在习得过程中以及在实验环节的早期增加了反应潜伏期。普萘洛尔在实验环节早期的习得部分也增加了反应潜伏期,但受影响的相关测量指标较少,并且与阿替洛尔(47%±13)相比,反应潜伏期增加的幅度较小(12%±5标准误)。测试剂量的盐酸苯环己哌啶(PCP)增加潜伏期的程度与阿替洛尔相同。PCP显著降低了准确性,而阿替洛尔或普萘洛尔则没有。在阿替洛尔作用下血压保持稳定,在普萘洛尔作用下血压下降约10 - 15毫米汞柱。未发现肾血管性高血压狒狒和正常血压狒狒在药物条件方面存在差异。药物作用不依赖于血浆普萘洛尔浓度。