Ghisolfi Eduardo S, Prokopiuk Alexandre S, Becker Jefferson, Ehlers João A, Belmonte-de-Abreu Paulo, Souza Diogo O, Lara Diogo R
Departamento de Bioqui;mica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, UFRGS, RS, Porto Alegre, Brazil.
Neuropsychopharmacology. 2002 Oct;27(4):629-37. doi: 10.1016/S0893-133X(02)00337-8.
In the p50 suppression paradigm, when two auditory stimuli are presented 500 ms apart, the amplitude of the second response (S2), compared with the first (S1), is markedly attenuated in healthy subjects. This is an index of sensory gating. Most schizophrenic patients fail to inhibit the p50 response to the second stimulus, which is assumed to reflect an inhibitory deficit. Adenosine is a neuromodulator with mostly inhibitory activity which is released by physiological stimuli. Since this inhibitory pattern resembles the phenomenon of sensory gating, the contribution of adenosine to p50 suppression was investigated in normal volunteers after treatment with the adenosine antagonist theophylline or placebo. P50 recordings were conducted in thirteen healthy subjects at baseline and 5, 30, 60, and 90 min after oral administration of theophylline (0.66 mg/kg, maximum dose of 500 mg) or placebo in a cross-over design. Baseline results from 17 drug-treated schizophrenic patients were included for comparison. Compared with placebo, theophylline treatment significantly increased P50 ratio (S2/S1) from 0.28 +/- 0.03 to 0.82 +/- 0.11 at 30 min and 0.61 +/- 0.07 at 60 min (mean +/- SEM), which were not significantly different from the schizophrenia group (0.74 +/- 0.05). The increased p50 ratio by theophylline was due to a combined decrease in S1 and increase in S2 amplitude. The impairment of p50 suppression by theophylline in normal subjects suggests a modulatory role of adenosine in sensory gating, which may be related to p50 suppression deficit in schizophrenia and is in agreement with a hypoadenosinergic model of schizophrenia.
在p50抑制范式中，当两个听觉刺激相隔500毫秒呈现时，与第一个反应（S1）相比，健康受试者中第二个反应（S2）的幅度会明显减弱。这是感觉门控的一个指标。大多数精神分裂症患者无法抑制对第二个刺激的p50反应，这被认为反映了抑制缺陷。腺苷是一种神经调节剂，主要具有抑制活性，由生理刺激释放。由于这种抑制模式类似于感觉门控现象，因此在用腺苷拮抗剂茶碱或安慰剂治疗后，在正常志愿者中研究了腺苷对p50抑制的作用。采用交叉设计，在13名健康受试者口服茶碱（0.66毫克/千克，最大剂量500毫克）或安慰剂后的基线以及5、30、60和90分钟时进行p50记录。纳入了17名接受药物治疗的精神分裂症患者的基线结果进行比较。与安慰剂相比，茶碱治疗在30分钟时显著提高了P50比值（S2/S1），从0.28±0.03提高到0.82±0.11，在60分钟时提高到0.61±0.07（平均值±标准误），与精神分裂症组（0.74±0.05）无显著差异。茶碱使p50比值增加是由于S1的联合降低和S2幅度的增加。茶碱在正常受试者中对p50抑制的损害表明腺苷在感觉门控中具有调节作用，这可能与精神分裂症中的p50抑制缺陷有关，并且与精神分裂症的低腺苷能模型一致。
