Swalve Natashia, Mulholland Michele M, Schulz Tiffany D, Li Ming
Department of Psychology, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Behav Pharmacol. 2016 Jun;27(4):321-30. doi: 10.1097/FBP.0000000000000199.
Patients with schizophrenia smoke cigarettes at a higher rate than the general population. We hypothesized that a factor in this comorbidity is sensitivity to the reinforcing and reinforcement-enhancement effects of nicotine. Phencyclidine (PCP) was used to model behavioral changes resembling negative symptoms of schizophrenia in rats. Ultrasonic vocalizations (USVs) in rats have been used to measure emotional states, with 50 kHz USVs indicating positive states and 22 kHz USVs indicating negative states. Total and categorized numbers of 22 and 50 kHz USVs and USVs during a visual stimulus (e.g. a potential measure of reinforcement-enhancement) were examined in rats following injection of PCP (2.0 mg/kg) and/or nicotine (0.2 or 0.4 mg/kg) daily for 7 days. PCP was then discontinued and all rats received nicotine (0.2 and 0.4 mg/kg) and PCP (2.0 mg/kg) on three challenge days. PCP acutely decreased 50 kHz vocalizations, whereas repeated nicotine potentiated rates of vocalizations, with similar patterns during light presentations. Rats in the PCP and nicotine combination groups made more 50 kHz vocalizations compared with rats in the control groups on challenge days. We conclude that PCP may produce a reward deficit, which is shown by decreased 50 kHz USVs, and behaviors post-PCP exposure may best model the comorbidity between schizophrenia and nicotine.
精神分裂症患者吸烟率高于普通人群。我们假设这种共病的一个因素是对尼古丁强化和增强强化作用的敏感性。苯环己哌啶(PCP)被用于在大鼠中模拟类似精神分裂症阴性症状的行为变化。大鼠的超声波发声(USV)已被用于测量情绪状态,50kHz的USV表示积极状态,22kHz的USV表示消极状态。在连续7天每天注射PCP(2.0mg/kg)和/或尼古丁(0.2或0.4mg/kg)后,检查大鼠在视觉刺激期间(例如强化增强的潜在测量指标)22kHz和50kHz USV的总数和分类数量以及USV。然后停用PCP,所有大鼠在三个挑战日接受尼古丁(0.2和0.4mg/kg)和PCP(2.0mg/kg)。PCP急性降低了50kHz的发声,而重复给予尼古丁则增强了发声率,在光照呈现期间有类似模式。在挑战日,PCP与尼古丁联合组的大鼠比对照组的大鼠发出更多50kHz的发声。我们得出结论,PCP可能产生奖励缺陷,这表现为50kHz USV减少,并且PCP暴露后的行为可能最能模拟精神分裂症与尼古丁之间的共病情况。