Departamento de Psicobiología y Neurociencias, Facultad de Psicología, Universidad Nacional Autónoma de México (UNAM), Av. Universidad 3004, Col. Copilco-Universidad, 04510, Mexico City, Mexico.
Departamento de Neurobiología, Dirección de Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente, México City, Mexico.
Psychopharmacology (Berl). 2017 Oct;234(20):3083-3090. doi: 10.1007/s00213-017-4692-8. Epub 2017 Jul 22.
Benzodiazepines are among the most widely prescribed and misused psychopharmaceutical drugs. Although they are well-tolerated, they are also capable of producing amnestic effects similar to those observed after pharmacological or organic cholinergic dysfunction. To date, the effect of benzodiazepine diazepam on the memory for discrimination of anticholinergic drugs has not been reported. The aim of the present study was to analyze the immediate and long-term effects of diazepam on a drug discrimination task with scopolamine. Male Wistar rats were trained to discriminate between scopolamine and saline administration using a two-lever discrimination task. Once discrimination was acquired, the subjects were divided into three independent groups, (1) control, (2) diazepam, and (3) diazepam chronic administration (10 days). Subsequently, generalization curves for scopolamine were obtained. Additionally, the diazepam and control groups were revaluated after 90 days without having been given any other treatment. The results showed that diazepam produced a significant reduction in the generalization gradient for scopolamine, indicating an impairment of discrimination. The negative effect of diazepam persisted even 90 days after drug had been administered. Meanwhile, the previous administration of diazepam for 10 days totally abated the generalization curve and the general performance of the subjects. The results suggest that diazepam affects memory for the stimulus discrimination of anticholinergic drugs and does so persistently, which could be an important consideration during the treatment of amnesic patients with benzodiazepines.
苯二氮䓬类药物是最广泛使用和滥用的精神药物之一。尽管它们耐受性良好，但也能够产生类似于药理学或有机胆碱能功能障碍后观察到的健忘效应。迄今为止，尚未报道苯二氮䓬类药物地西泮对抗胆碱能药物的记忆辨别作用的影响。本研究的目的是分析地西泮对东莨菪碱药物辨别任务的即时和长期影响。雄性 Wistar 大鼠通过双杠辨别任务训练辨别东莨菪碱和生理盐水给药。一旦获得辨别能力，将研究对象分为三组，（1）对照组，（2）地西泮组，（3）地西泮慢性给药组（10 天）。随后，获得了东莨菪碱的概括曲线。此外，在没有给予任何其他治疗的情况下，90 天后再次评估地西泮和对照组。结果表明，地西泮显著降低了东莨菪碱的概括梯度，表明辨别能力受损。即使在停药 90 天后，地西泮的负面影响仍然存在。同时，地西泮连续给药 10 天完全消除了受试者的概括曲线和一般表现。结果表明，地西泮影响抗胆碱能药物刺激辨别记忆，且具有持续性，这在治疗记忆障碍患者时应予以考虑。
