Krishnan-Sarin S, Jing S L, Kurtz D L, Zweifel M, Portoghese P S, Li T K, Froehlich J C
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202, USA.
Psychopharmacology (Berl). 1995 Jul;120(2):177-85. doi: 10.1007/BF02246191.
This study demonstrates that the selective delta receptor antagonists ICI 174864 and naltrindole (NTI) attenuate alcohol intake in a dose-dependent manner, without altering water intake, in rats selectively bred for alcohol preference. ICI 174864 had a very limited duration of action, as evidenced by the fact that suppression of alcohol intake lasted for only an hour following ICI 174864 administration. NTI, when administered in a dose of 10 mg/kg, suppressed alcohol intake by 28%. Increasing the dose of NTI to 15 mg/kg produced a 44% suppression of alcohol intake, but a further increase to 20 mg/kg did not produce greater suppression than was seen with a dose of 15 mg/kg (46% versus 44%, respectively). This suggests that NTI is maximally effective in suppressing alcohol intake at a dose of 15.0 mg/kg. NTI displayed a long duration of action, as evidenced by attenuation of alcohol drinking that lasted for at least 8 h following drug treatment. Administering the maximally effective dose of NTI (15 mg/kg) in two parts, separated by 4 h, served to prolong the duration of action of NTI and produced an attenuation of alcohol intake, but not water intake, that lasted for at least 28 h. The effect of NTI on alcohol intake was not specific for alcohol, as evidenced by the fact that NTI reduced the intake of saccharin solutions with and without alcohol.
本研究表明,选择性δ受体拮抗剂ICI 174864和纳曲吲哚(NTI)能以剂量依赖的方式减少选择性培育的嗜酒大鼠的酒精摄入量,而不改变其饮水量。ICI 174864的作用持续时间非常有限,这一点从给予ICI 174864后酒精摄入量的抑制仅持续一小时这一事实可以看出。当以10毫克/千克的剂量给予NTI时,酒精摄入量减少了28%。将NTI的剂量增加到15毫克/千克,酒精摄入量减少了44%,但进一步增加到20毫克/千克时,其抑制作用并不比15毫克/千克时更强(分别为46%对44%)。这表明NTI在剂量为15.0毫克/千克时对抑制酒精摄入最为有效。NTI显示出较长的作用持续时间,药物治疗后酒精摄入量的减少持续至少8小时即证明了这一点。将NTI的最大有效剂量(15毫克/千克)分两部分给药,间隔4小时,可延长NTI的作用持续时间,并使酒精摄入量减少,但不影响饮水量,这种减少持续至少28小时。NTI对酒精摄入量的影响并非酒精特有的,因为NTI减少了含酒精和不含酒精的糖精溶液的摄入量。