Turgeon S M, Auerbach E A, Duncan-Smith M K, George J R, Graves W W
Department of Psychology, Amherst College, Amherst, MA 01002, USA.
Pharmacol Biochem Behav. 2000 Jul;66(3):533-9. doi: 10.1016/s0091-3057(00)00223-9.
The delayed effects of phencyclidine (PCP) have been shown to disrupt latent inhibition (LI) in a conditioned taste-aversion paradigm. In an attempt to understand the mechanism of this disruption, the delayed effects of the selective sigma receptor agonist 1,3-Di(2-tolyl)guanidine (DTG) and the selective NMDA receptor antagonist MK-801 on latent inhibition were assessed in the same paradigm. Water-deprived male rats were allowed access to either water (nonpreexposed; NPE) or 5% sucrose (preexposed; PE) for 30 min on 2 consecutive days. On the third day, animals were allowed access to sucrose and subsequently injected with lithium chloride. On the forth day, animals were allowed access to both sucrose and water. LI was assessed by comparing the percent sucrose consumed in PE and NPE groups on the fourth day. DTG (1.0, 5.0, or 10.0 mg/kg), MK-801 (0.5, 1.0, or 2.0 mg/kg), or vehicle was administered IP 20 h before preexposure (days 1 and 2) and conditioning (day 3). In vehicle-treated groups, PE animals consumed a significantly higher percent sucrose on the test day than NPE animals, indicating the presence of LI. DTG (10.0 mg/kg) and MK-801 (2.0 mg/kg) decreased the percent sucrose consumed by animals in the PE group to the level observed in the NPE group, indicating disrupted LI. However, this dose of MK-801 was found to produce a decrease in percent sucrose consumed in PE animals not treated with lithium chloride, indicating that the decrease observed in the LI paradigm could be due to MK-801-induced decrease in taste preference for sucrose rather than a disruption of LI. Lower doses of MK-801 that did not produce a decrease in taste preference for sucrose did not significantly disrupt LI. None of the doses of DTG tested altered taste preference for sucrose. These data suggest a role for sigma receptors in the previously observed PCP-induced disruption of LI. Published by Elsevier Science Inc., 2000
已证明苯环利定（PCP）的延迟效应会在条件性味觉厌恶范式中破坏潜伏抑制（LI）。为了试图理解这种破坏的机制，在同一范式中评估了选择性西格玛受体激动剂1,3 - 二（2 - 甲苯基）胍（DTG）和选择性NMDA受体拮抗剂MK - 801的延迟效应对潜伏抑制的影响。让缺水的雄性大鼠连续两天每天有30分钟时间接触水（未预先接触；NPE）或5%蔗糖（预先接触；PE）。在第三天，让动物接触蔗糖，随后注射氯化锂。在第四天，让动物接触蔗糖和水。通过比较第四天PE组和NPE组消耗的蔗糖百分比来评估潜伏抑制。在预先接触（第1天和第2天）和条件作用（第3天）前20小时腹腔注射DTG（1.0、5.0或10.0毫克/千克）、MK - 801（0.5、1.0或2.0毫克/千克）或赋形剂。在赋形剂处理组中，PE动物在测试日消耗的蔗糖百分比显著高于NPE动物，表明存在潜伏抑制。DTG（10.0毫克/千克）和MK - 801（2.0毫克/千克）使PE组动物消耗的蔗糖百分比降至NPE组观察到的水平，表明潜伏抑制被破坏。然而，发现该剂量的MK - 801会使未用氯化锂处理的PE动物消耗的蔗糖百分比降低，这表明在潜伏抑制范式中观察到的降低可能是由于MK - 801导致对蔗糖的味觉偏好降低，而不是潜伏抑制的破坏。未导致对蔗糖味觉偏好降低的较低剂量的MK - 801并未显著破坏潜伏抑制。所测试的DTG的任何剂量均未改变对蔗糖的味觉偏好。这些数据表明西格玛受体在先前观察到的PCP诱导的潜伏抑制破坏中起作用。由爱思唯尔科学公司出版，2000年
