Gatto G J, Grant K A
Department of Physiology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1083, USA.
Behav Pharmacol. 1997 Jun;8(2-3):139-46.
The aim of the present study was to investigate whether ethanol training affects the ability of Ro 15-4513 to block the discriminative stimulus effects of ethanol dose differentially. Three different groups of rats were trained to discriminate 1.0 g/kg ethanol (n = 8), 1.5 g/kg ethanol (n = 7) or 2.0 g/kg ethanol (n = 8) from water in a two-lever, food-reinforced procedure. Ethanol and water were administered by gavage 20 min before the onset of the session. When the discrimination performance was stable, rats were pretreated with Ro 15-4513 (1-17 mg/kg; i.p.) 5 min before the administration of ethanol. Ro 15-4513 attenuated the discriminative stimulus effects of 1.0 and 1.5 g/kg ethanol but not 2.0 g/kg ethanol in each of the ethanol training groups. Overall, blockade of the discriminative stimulus effects of 1.0 and 1.5 g/kg ethanol by 5.6 mg/kg Ro 15-4513 occurred without significantly altering response rates or blood ethanol concentrations. A decrease in blood ethanol concentration was, however, found with 17 mg/kg Ro 15-4513 in combination with 2.0 g/kg ethanol. These results suggest that the benzodiazepine partial inverse agonist, Ro 15-4513, can attenuate the discriminative stimulus effects associated with low to moderate doses of ethanol (1.0-1.5 g/kg).
本研究的目的是调查乙醇训练是否会不同程度地影响Ro 15 - 4513阻断乙醇剂量辨别刺激效应的能力。三组不同的大鼠在双杠杆食物强化程序中接受训练，以区分1.0 g/kg乙醇（n = 8）、1.5 g/kg乙醇（n = 7）或2.0 g/kg乙醇与水。在实验开始前20分钟通过灌胃给予乙醇和水。当辨别性能稳定后，在给予乙醇前5分钟给大鼠腹腔注射Ro 15 - 4513（1 - 17 mg/kg）。在每个乙醇训练组中，Ro 15 - 4513减弱了1.0和1.5 g/kg乙醇的辨别刺激效应，但对2.0 g/kg乙醇没有影响。总体而言，5.6 mg/kg的Ro 15 - 4513阻断1.0和1.5 g/kg乙醇的辨别刺激效应时，并未显著改变反应率或血液乙醇浓度。然而，发现17 mg/kg的Ro 15 - 4513与2.0 g/kg乙醇联合使用时会使血液乙醇浓度降低。这些结果表明，苯二氮䓬类部分反向激动剂Ro 15 - 4513可以减弱与低至中等剂量乙醇（1.0 - 1.5 g/kg）相关的辨别刺激效应。
