Bielajew Catherine, Diotte Magali, Milairessis Eleftherios
School of Psychology, University of Ottawa, Ont., Ottawa, Canada K1N 6N5.
Behav Brain Res. 2003 Jul 14;143(1):75-83. doi: 10.1016/s0166-4328(03)00004-4.
The effects of naloxone on the rewarding and aversive properties of brain stimulation derived from the ventral tegmental area and the nucleus reticularis gigantocellularis, respectively, were assessed in rats, based on the following measures-the current threshold for latency to escape aversive nucleus reticularis gigantocellularis stimulation, the frequency threshold for rewarding ventral tegmental area stimulation, and the frequency threshold for self-stimulation obtained from delivery of concurrent ventral tegmental area and nucleus reticularis gigantocellularis stimulation, before and after three systemic doses of naloxone (0, 10, and 20mg/kg); in the latter case, the stimulation trains were interdigitated with an interpulse interval of 2 ms. Initially, thresholds for concurrent stimulation were elevated relative to the values obtained for ventral tegmental area stimulation alone, returning to baseline values only when the nucleus reticularis gigantocellularis stimulation no longer induced escape. After each pairing of the two sites, the current threshold for escape gradually increased until the maximum value administered, 700 microA, at which point aversive responses were no longer observed. This required very few pairings, between one and five trials across animals. Drug tests were then begun and produced a significant dose-response threshold increase across animals, without reinstating the latency to escape nucleus reticularis gigantocellularis stimulation. These findings are discussed in terms of a dissociation between the analgesic and rewarding properties of ventral tegmental area stimulation.
基于以下指标,分别评估了纳洛酮对源自大鼠腹侧被盖区和巨细胞网状核的脑刺激奖赏性和厌恶性特性的影响:逃避巨细胞网状核厌恶性刺激的潜伏期电流阈值、腹侧被盖区奖赏性刺激的频率阈值,以及在给予三次全身剂量的纳洛酮(0、10和20mg/kg)前后,同时给予腹侧被盖区和巨细胞网状核刺激时的自我刺激频率阈值;在后一种情况下,刺激序列以2毫秒的脉冲间隔交错排列。最初,同时刺激的阈值相对于单独腹侧被盖区刺激所获得的值升高,只有当巨细胞网状核刺激不再诱发逃避时才恢复到基线值。在两个部位每次配对后,逃避的电流阈值逐渐增加,直至达到所施加的最大值700微安,此时不再观察到厌恶性反应。这在动物中只需进行一到五次试验,很少的配对次数。然后开始药物测试,结果显示动物的剂量-反应阈值显著增加,同时并未恢复逃避巨细胞网状核刺激的潜伏期。根据腹侧被盖区刺激的镇痛和奖赏特性之间的分离对这些发现进行了讨论。