Mactutus Charles F, Harrod Steven B, Hord Lauren L, Moran Landhing M, Booze Rosemarie M
Behavioral Neuroscience Program, Department of Psychology, University of South Carolina Columbia, SC, USA.
Front Psychiatry. 2011 Jun 28;2:38. doi: 10.3389/fpsyt.2011.00038. eCollection 2011.
One clue regarding the basis of cocaine-induced deficits in attentional processing is provided by the clinical findings of changes in the infants' startle response; observations buttressed by neurophysiological evidence of alterations in brainstem transmission time. Using the IV route of administration and doses that mimic the peak arterial levels of cocaine use in humans, the present study examined the effects of prenatal cocaine on auditory information processing via tests of the auditory startle response (ASR), habituation, and prepulse inhibition (PPI) in the offspring. Nulliparous Long-Evans female rats, implanted with an IV access port prior to breeding, were administered saline, 0.5, 1.0, or 3.0 mg/kg/injection of cocaine HCL (COC) from gestation day (GD) 8-20 (1×/day-GD8-14, 2×/day-GD15-20). COC had no significant effects on maternal/litter parameters or growth of the offspring. At 18-20 days of age, one male and one female, randomly selected from each litter displayed an increased ASR (>30% for males at 1.0 mg/kg and >30% for females at 3.0 mg/kg). When reassessed in adulthood (D90-100), a linear dose-response increase was noted on response amplitude. At both test ages, within-session habituation was retarded by prenatal cocaine treatment. Testing the females in diestrus vs. estrus did not alter the results. Prenatal cocaine altered the PPI response function across interstimulus interval and induced significant sex-dependent changes in response latency. Idazoxan, an α(2)-adrenergic receptor antagonist, significantly enhanced the ASR, but less enhancement was noted with increasing doses of prenatal cocaine. Thus, in utero exposure to cocaine, when delivered via a protocol designed to capture prominent features of recreational usage, causes persistent, if not permanent, alterations in auditory information processing, and suggests dysfunction of the central noradrenergic circuitry modulating, if not mediating, these responses.
关于可卡因导致注意力加工缺陷的基础，婴儿惊吓反应变化的临床发现提供了一条线索；脑干传导时间改变的神经生理学证据支持了这些观察结果。本研究采用静脉给药途径和模拟人类使用可卡因时动脉血药峰值水平的剂量，通过对后代的听觉惊吓反应（ASR）、习惯化和前脉冲抑制（PPI）测试，研究了产前可卡因对听觉信息加工的影响。未生育的长 Evans 雌性大鼠在繁殖前植入静脉通路端口，从妊娠第 8 天至第 20 天给予生理盐水、0.5、1.0 或 3.0 mg/kg/注射的盐酸可卡因（COC）（妊娠第 8 - 14 天每天 1 次，妊娠第 15 - 20 天每天 2 次）。COC 对母体/窝仔参数或后代生长没有显著影响。在 18 - 20 日龄时，从每窝中随机选择一只雄性和一只雌性，其 ASR 增加（1.0 mg/kg 时雄性增加>30%，3.0 mg/kg 时雌性增加>30%）。在成年期（第 90 - 100 天）重新评估时，反应幅度呈现线性剂量反应增加。在两个测试年龄，产前可卡因治疗均延迟了实验过程中的习惯化。在动情间期与动情期对雌性进行测试并未改变结果。产前可卡因改变了跨刺激间隔的 PPI 反应功能，并在反应潜伏期诱导了显著的性别依赖性变化。咪唑克生，一种α(2) - 肾上腺素能受体拮抗剂，显著增强了 ASR，但随着产前可卡因剂量增加，增强作用减弱。因此，子宫内暴露于可卡因，当通过旨在捕捉娱乐性使用突出特征的方案给药时，会导致听觉信息加工持续（即使不是永久性）改变，并提示调节（如果不是介导）这些反应的中枢去甲肾上腺素能神经回路功能障碍。
