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大鼠乙醇戒断期间尼古丁替代对戊四氮辨别刺激的性别差异。

Sex differences in nicotine substitution to a pentylenetetrazol discriminative stimulus during ethanol withdrawal in rats.

作者信息

Jung M E, Wallis C J, Gatch M B, Lal H

机构信息

Department of Pharmacology, University of North Texas Health Science Center, Fort Worth 76107-2699, USA.

出版信息

Psychopharmacology (Berl). 2000 Apr;149(3):235-40. doi: 10.1007/s002130000392.

DOI:10.1007/s002130000392
PMID:10823403
Abstract

RATIONALE

Nicotine and ethanol are frequently co-abused in men and women, but few studies compare common stimulus effects produced by these substances between males and females.

OBJECTIVES

This study compared the anxiety-like behavior induced by nicotine prior to and during ethanol withdrawal in intact male, sham-operated female, and ovariectomized (OVX) rats.

METHODS

Using an animal model of anxiety, the pentylenetetrazol (PTZ) drug-discrimination assay, rats were trained to discriminate PTZ (16 mg/kg, i.p.) from saline and were subjected to the following tests: (1) PTZ-lever selection at 12 h after termination of ethanol diet (4.5% for 10 days); (2) dose-response tests for nicotine (0.08-1.3 mg/kg) prior to ethanol and 1.5, 6, and 7 days after ethanol withdrawal.

RESULTS

(1) During acute ethanol withdrawal (12 h), more male rats (43.4%) responded on the PTZ lever than OVX (29%) or sham female (15.3%) rats. (2) For nicotine dose-response tests, more male rats (70%) selected the PTZ lever than OVX (37.5%) or sham female (50%) rats prior to ethanol. At 1.5 days, nicotine fully generalized to the PTZ stimulus in male (100%) and OVX (90%), but only partially in sham female (50%) rats. At 6 days and 7 days after ethanol withdrawal, the PTZ-lever selection decreased, but more male rats (78%) tended to respond on a PTZ lever than OVX (63.6%) or sham female rats (62.5%).

CONCLUSIONS

Acute nicotine produces anxiety-like behavior similar to that of PTZ in male and female rats, and this effect of nicotine is intensified during ethanol withdrawal in male and OVX rats, but not in sham female rats.

摘要

理论依据

男性和女性中经常同时滥用尼古丁和乙醇,但很少有研究比较这些物质在男性和女性之间产生的共同刺激效应。

目的

本研究比较了完整雄性、假手术雌性和去卵巢(OVX)大鼠在乙醇戒断前和戒断期间尼古丁诱导的焦虑样行为。

方法

使用焦虑动物模型,即戊四氮(PTZ)药物辨别试验,训练大鼠区分腹腔注射PTZ(16mg/kg)和生理盐水,并进行以下测试:(1)乙醇饮食(4.5%,持续10天)终止后12小时的PTZ杠杆选择;(2)乙醇戒断前和戒断后1.5、6和7天对尼古丁(0.08-1.3mg/kg)的剂量反应测试。

结果

(1)在急性乙醇戒断(12小时)期间,选择PTZ杠杆的雄性大鼠(43.4%)比OVX大鼠(29%)或假手术雌性大鼠(15.3%)更多。(2)对于尼古丁剂量反应测试,乙醇戒断前选择PTZ杠杆的雄性大鼠(70%)比OVX大鼠(37.5%)或假手术雌性大鼠(50%)更多。在1.5天时,尼古丁在雄性(100%)和OVX大鼠(90%)中完全泛化为PTZ刺激,但在假手术雌性大鼠中仅部分泛化(50%)。在乙醇戒断后6天和7天,PTZ杠杆选择减少,但选择PTZ杠杆的雄性大鼠(78%)仍比OVX大鼠(63.6%)或假手术雌性大鼠(62.5%)更多。

结论

急性尼古丁在雄性和雌性大鼠中产生与PTZ类似的焦虑样行为,并且尼古丁的这种作用在雄性和OVX大鼠乙醇戒断期间增强,但在假手术雌性大鼠中未增强。

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Psychopharmacology (Berl). 2000 Apr;149(3):235-40. doi: 10.1007/s002130000392.
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