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血管舒张剂肼屈嗪的辨别刺激特性:与α1和α2肾上腺素能受体药物的差异泛化

Discriminative stimulus properties of the vasodilator, hydralazine: differential generalization with alpha 1 and alpha 2 adrenoreceptor drugs.

作者信息

Bennett D A, Lal H

出版信息

Prog Neuropsychopharmacol Biol Psychiatry. 1982;6(1):17-26. doi: 10.1016/s0364-7722(82)80103-3.

Abstract
  1. Male albino rats were trained to an operant procedure of lever pressing on an FR-10 schedule of food reinforcement to respond on one lever located on one side of the food cup after an injection of hydralazine (1,25 mg/kg), and to respond on an alternate lever located on the other side of the food cup after an injection of saline. 2. Seven out of ten rats learned the hydralazine-saline discrimination to the rigid criterion of selecting the correct lever for reinforcement on ten consecutive sessions. 3. The elicitation of the discriminative stimulus was dose-dependent (r = 0,98; p less than .001) with 100, 43, and 14% of the subjects selecting the hydralazine lever following hydralazine doses of 1,25; 0,32 and 0,08 mg/kg, respectively (ED50, 0,28 mg/kg). 4. A reduction in response rate and blood pressure was noted only at the 1.25 mg/kg dose. 5. No tolerance to the hypotensive effect of hydralazine was found. 6. In generalization tests, prazosin, an alpha 1 antagonist, was found to produce a dose-dependent generalization to hydralazine (ED50, 1, 25 mg/kg) while clonidine, an alpha 2 agonist, did not generalize. 7. These data indicate that hydralazine produces a discriminable interoceptive stimulus exact site of action of which is not known.
摘要
  1. 雄性白化大鼠接受训练,采用按食物强化的FR - 10程序进行杠杆按压操作。注射肼屈嗪(1.25毫克/千克)后,在食物杯一侧的一个杠杆上做出反应;注射生理盐水后,在食物杯另一侧的另一个杠杆上做出反应。2. 十只大鼠中有七只学会了肼屈嗪 - 生理盐水辨别,达到了在连续十次实验中选择正确杠杆以获得强化的严格标准。3. 辨别性刺激的诱发呈剂量依赖性(r = 0.98;p小于0.001),在注射1.25、0.32和0.08毫克/千克的肼屈嗪后,分别有100%、43%和14%的实验对象选择肼屈嗪杠杆(半数有效剂量,0.28毫克/千克)。4. 仅在1.25毫克/千克剂量时观察到反应率和血压降低。5. 未发现对肼屈嗪降压作用产生耐受性。6. 在泛化试验中,发现α1拮抗剂哌唑嗪对肼屈嗪产生剂量依赖性泛化(半数有效剂量,1.25毫克/千克),而α2激动剂可乐定则未产生泛化。7. 这些数据表明,肼屈嗪产生了一种可辨别的内感受性刺激,其确切作用部位尚不清楚。

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