Gay M H, Ryan G P, Boisse N R, Guarino J J
Eur J Pharmacol. 1983 Nov 11;95(1-2):21-9. doi: 10.1016/0014-2999(83)90263-7.
A rat model of phenobarbital tolerance and physical dependence has been developed based on the 'maximally tolerable, chronically equivalent' dosing paradigm. Sodium phenobarbital was administered orally twice daily for 35 days in individually adjusted doses to achieve mean daily peak CNS depression culminating in severe ataxia. Dose to dose continuity of CNS depression was maintained throughout treatment. At the time of dosing rats were mildly ataxic. Following abrupt termination of chronic treatment, an abstinence syndrome characterized by CNS hyperexcitability was observed, which demonstrates physical dependence. Signs, which included motor, autonomic, and behavioral manifestations, appeared from 12-24 h and animals recovered by 12 days. Although tolerance development was nearly complete on day 10 of treatment, the abstinence syndrome observed was more severe following 35 than after 10 days of chronic treatment. Characteristics of tolerance and physical dependence are similar to those described for other species including humans.
基于“最大耐受、长期等效”给药模式，已建立了苯巴比妥耐受性和身体依赖性的大鼠模型。苯巴比妥钠以个体化调整剂量每日口服两次，持续35天，以达到每日平均中枢神经系统抑制峰值，最终导致严重共济失调。在整个治疗过程中保持中枢神经系统抑制的剂量间连续性。给药时大鼠有轻度共济失调。在长期治疗突然终止后，观察到以中枢神经系统过度兴奋为特征的戒断综合征，这表明存在身体依赖性。症状包括运动、自主神经和行为表现，在12 - 24小时出现，动物在12天内恢复。虽然在治疗第10天时耐受性发展几乎完成，但与10天慢性治疗相比，35天慢性治疗后观察到的戒断综合征更严重。耐受性和身体依赖性的特征与包括人类在内的其他物种所描述的相似。
