Alexander R C, Wright R, Freed W
Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania, Philadelphia, USA.
Neuropsychopharmacology. 1996 Nov;15(5):484-90. doi: 10.1016/S0893-133X(96)00058-9.
Phencyclidine (PCP) and amphetamine (AMP) can induce psychotic syndromes in humans, whereas administration of these drugs to mice results in behavioral activation that is influenced by genetic factors. Quantitative trait loci (QTL) underlying genetic differences in response to PCP and AMP in mice were provisionally identified by correlating allelic variation at known marker loci in the BXD series of recombinant inbred (RI) mice and its progenitors (C57BL/6J and DBA/2J inbred strains) with the locomotor response of each strain to PCP and AMP. Total distance traveled for individual mice from each of the 26 BXD RI and two progenitor strains was measured after injections of normal saline and 7.5 mg/kg i.p. injection of PCP. This procedure was repeated after 1 week, using 5.0 mg/kg of AMP, instead of PCP. Markers significantly (p < .01) correlated with response to PCP map to murine chromosomes 1, 14, and 15. Response to amphetamine was correlated with markers mapping to chromosomes 4, 5, 6, 8, 14, and 18. Identification of the QTL underlying PCP-induced and AMP-induced behavior in mice may provide clues into the complicated genetics of psychosis in humans.
苯环己哌啶（PCP）和苯丙胺（AMP）可在人类中诱发精神病综合征，而给小鼠施用这些药物会导致行为激活，且这种激活受遗传因素影响。通过将重组近交（RI）小鼠BXD系列及其亲本（近交系C57BL/6J和DBA/2J）中已知标记位点的等位基因变异与每个品系对PCP和AMP的运动反应相关联，初步确定了小鼠对PCP和AMP反应的遗传差异背后的数量性状基因座（QTL）。给26个BXD RI品系和两个亲本品系的每只小鼠腹腔注射生理盐水以及7.5mg/kg的PCP后，测量每只小鼠的总移动距离。1周后重复此过程，使用5.0mg/kg的AMP代替PCP。与对PCP的反应显著相关（p < 0.01）的标记定位于小鼠的1号、14号和15号染色体。对苯丙胺的反应与定位于4号、5号、6号、8号、14号和18号染色体的标记相关。确定小鼠中PCP诱导和AMP诱导行为背后的QTL可能为人类精神病复杂的遗传学提供线索。
