Malatynska E, De Leon I, Allen D, Yamamura H I
University of Arizona, College of Medicine, Department of Pharmacology, Tucson 85724, USA.
Brain Res Bull. 1995;37(1):53-9. doi: 10.1016/0361-9230(94)00257-6.
The dominant-submissive relationship established between two rats competing for food is a model of depression and is used here to divide animals into two behaviorally distinct groups. Basal and GABA-stimulated 36CI- uptake was investigated for both dominant and submissive rats as well as the in vitro effect of the antidepressant amitriptyline (AMI). Because the antidepressant action of AMI only appears after chronic treatment, the effect of chronic injections of AMI on these behavioral and biochemical measures was also studied. Basal 36CI- uptake is significantly higher for dominant rats than for submissive rats. Increasing concentrations of AMI added to membrane vesicles enhanced 30 microM GABA-stimulated chloride uptake for dominant rats and inhibited it for submissive rats. Chronic treatment of dominant and submissive rats with AMI reversed these in vitro effects. The biochemical data correspond to the changes of the rats behavior in the dominance test after chronic treatment with AMI. However, this correlation is more clear for dominant than for submissive rats. Specific chloride influx was used as a measure of the sensitivity of GABAA receptor to GABA. This revealed different sensitivity states for GABAA receptors in tissues obtained from dominant and submissive rats. It is possible that the distinct conformational states of GABAA receptor are responsible for differences in rats behavior and in vitro effects of AMI before and after in vivo treatment of rats with this anti-depressant.
两只争夺食物的大鼠之间建立的主导-从属关系是一种抑郁症模型，在此用于将动物分为行为上不同的两组。研究了主导和从属大鼠的基础及γ-氨基丁酸（GABA）刺激的³⁶Cl⁻摄取，以及抗抑郁药阿米替林（AMI）的体外效应。由于AMI的抗抑郁作用仅在慢性治疗后才出现，还研究了慢性注射AMI对这些行为和生化指标的影响。主导大鼠的基础³⁶Cl⁻摄取显著高于从属大鼠。添加到膜囊泡中的AMI浓度增加，增强了主导大鼠³⁰微摩尔GABA刺激的氯摄取，而抑制了从属大鼠的这种摄取。用AMI对主导和从属大鼠进行慢性治疗可逆转这些体外效应。生化数据与慢性用AMI治疗后大鼠在优势度测试中的行为变化相对应。然而，这种相关性在主导大鼠中比在从属大鼠中更明显。特异性氯内流用作GABAA受体对GABA敏感性的指标。这揭示了从主导和从属大鼠获得的组织中GABAA受体的不同敏感状态。有可能GABAA受体的不同构象状态是大鼠行为差异以及用这种抗抑郁药对大鼠进行体内治疗前后AMI体外效应差异的原因。
