Department of Psychology, Amherst College, Amherst, MA 01002, USA.
Pharmacol Biochem Behav. 2010 Apr;95(2):173-8. doi: 10.1016/j.pbb.2010.01.001. Epub 2010 Jan 18.
Previous research in our laboratory indicates that the psychotomimetic drug phencyclidine (PCP) reduces voluntary sucrose consumption in male rats, potentially modeling the schizophrenic symptom of anhedonia. Given reports from the clinical literature that schizophrenia has a later age of onset and more favorable outcome in females, PCP might be expected to have sexually dimorphic effects in animal models of schizophrenia such as PCP-induced decreases in voluntary sucrose consumption. Young adult (66 days old) and adult (109 days old) male and female rats were trained to drink sucrose during a 30 min/day presentation protocol. On the day prior to the test day, animals were treated with PCP (15 mg/kg) or saline four hours after the onset of the sucrose presentation (20 h prior to the sucrose on the test day). PCP decreased sucrose consumption on the test day similarly in adult males and females, although females also showed decreased water consumption. In young animals, PCP decreased sucrose consumption in males but not in females. These results are consistent with the prediction that females will be less sensitive to the schizophrenia-like behavioral effects of PCP. In a separate study, the same animals were tested in an elevated plus maze one to two months after testing for voluntary sucrose consumption. Significant sex x drug interaction effects on a number of measures in the elevated plus maze indicated that prior exposure to PCP had an anxiolytic effect in females and an anxiogenic effect in males. While unexpected, this finding indicates an additional sexually dimorphic effect of PCP on behavior and its potential relevance to the PCP model of schizophrenia is discussed.
先前我们实验室的研究表明,致幻剂苯环已哌啶(PCP)可减少雄性大鼠的自愿性蔗糖摄入量,这可能模拟了精神分裂症快感缺失的症状。鉴于临床文献中的报告称,精神分裂症在女性中的发病年龄较晚且预后较好,PCP 可能会在精神分裂症的动物模型中产生性别二态效应,例如 PCP 引起的自愿性蔗糖摄入量减少。年轻成年(66 天大)和成年(109 天大)雄性和雌性大鼠在每天 30 分钟的呈现方案中接受蔗糖饮用训练。在测试日之前的一天,动物在蔗糖呈现开始后的四个小时(测试日的蔗糖前 20 小时)接受 PCP(15 mg/kg)或生理盐水治疗。PCP 相似地减少了成年雄性和雌性大鼠在测试日的蔗糖摄入量,尽管雌性大鼠的饮水量也有所减少。在年轻动物中,PCP 减少了雄性大鼠的蔗糖摄入量,但未减少雌性大鼠的蔗糖摄入量。这些结果与女性对 PCP 类似精神分裂症行为效应的敏感性较低的预测一致。在一项单独的研究中,同一批动物在自愿性蔗糖消耗测试后一到两个月在高架十字迷宫中进行测试。高架十字迷宫中多项测量的显著性别 x 药物相互作用效应表明,先前暴露于 PCP 对雌性具有抗焦虑作用,而对雄性具有焦虑作用。虽然出乎意料,但这一发现表明 PCP 对行为具有额外的性别二态效应,及其与 PCP 精神分裂症模型的潜在相关性将在讨论中进一步阐述。