Jung M E, Wallis C J, Gatch M B, Lal H
Department of Pharmacology and Substance Abuse Institute of North Texas, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas, USA.
J Pharmacol Exp Ther. 1999 Nov;291(2):576-82.
This study investigated sex differences in responding to the pentylenetetrazol (PTZ, a gamma-aminobutyric acid A antagonist) discriminative stimulus and to substitution to PTZ during ethanol withdrawal. The PTZ stimulus has served as an anxiogenic stimulus in numerous studies. Adult male and female rats were trained to discriminate PTZ (16 mg/kg i.p.) from saline in a two-lever food-reinforced task. They were then gonadectomized or sham-operated. Ovariectomized (OVX) rats were also tested during 17beta-estradiol (2.5 mg, 21 days release, s.c.) replacement. The PTZ dose response (0-16 mg/kg i.p.) was tested in all groups. In general, fewer females than males responded to PTZ. Diazepam (DZP; 0-10 mg/kg i.p.) injected before PTZ (16 mg/kg) decreased the number of rats selecting the PTZ lever. This effect was greater in sham female and estradiol-replaced-OVX rats than in male or OVX rats. Rats then received chronic ethanol diet (6.5%) for 10 days. During ethanol withdrawal (12 h after termination of the ethanol diet), they were tested for PTZ lever selection. PTZ lever selection differed between groups: sham or castrated male rats > OVX > sham female or estradiol-replaced-OVX rats. In sham female rats, estradiol concentrations showed a cyclic pattern with an estradiol surge that did not influence their PTZ discrimination performance. After i.p. injection of ethanol (2 g/kg), blood ethanol concentrations were not different in male and female rats. These findings suggest that 1) female rats are less sensitive to the anxiogenic effects of PTZ; 2) female rats are less sensitive to the anxiogenic effects of ethanol withdrawal; and 3) estrogen plays some role in mediation of these sex differences.
本研究调查了在对戊四氮（PTZ，一种γ-氨基丁酸A拮抗剂）辨别刺激的反应以及乙醇戒断期间对PTZ替代物的反应中的性别差异。在众多研究中，PTZ刺激已被用作一种致焦虑刺激。成年雄性和雌性大鼠在双杠杆食物强化任务中接受训练，以区分PTZ（腹腔注射16mg/kg）和生理盐水。然后对它们进行去势或假手术。卵巢切除（OVX）大鼠在接受17β-雌二醇（2.5mg，21天缓释，皮下注射）替代治疗期间也进行了测试。对所有组都测试了PTZ剂量反应（腹腔注射0 - 16mg/kg）。一般来说，对PTZ有反应的雌性大鼠比雄性大鼠少。在PTZ（16mg/kg）之前注射地西泮（DZP；腹腔注射0 - 10mg/kg）减少了选择PTZ杠杆的大鼠数量。这种效应在假手术雌性大鼠和雌二醇替代的OVX大鼠中比在雄性或OVX大鼠中更大。然后大鼠接受为期10天的慢性乙醇饮食（6.5%）。在乙醇戒断期间（乙醇饮食终止后12小时），测试它们对PTZ杠杆的选择。不同组之间PTZ杠杆选择存在差异：假手术或去势雄性大鼠>OVX>假手术雌性或雌二醇替代的OVX大鼠。在假手术雌性大鼠中，雌二醇浓度呈现出一种循环模式，伴有雌二醇激增，但这并不影响它们的PTZ辨别性能。腹腔注射乙醇（2g/kg）后，雄性和雌性大鼠的血液乙醇浓度没有差异。这些发现表明：1）雌性大鼠对PTZ的致焦虑作用较不敏感；2）雌性大鼠对乙醇戒断的致焦虑作用较不敏感；3）雌激素在介导这些性别差异中起一定作用。
