Hegarty A A, Vogel W H
Department of Pharmacology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Pharmacol Biochem Behav. 1995 Dec;52(4):771-8. doi: 10.1016/0091-3057(95)00177-x.
The mesocortical dopamine system is thought to play an important role in the etiology of the stress response. Dopamine (DA) has been shown to accumulate in the rat frontal cortex in response to a wide variety of stressors. Diazepam, an anxiolytic benzodiazepine, can reverse the effects of stress on cortical DA. We investigated the effects of acute and chronic diazepam administration on immobilization stress-induced changes of the DA system in the frontal cortex of the rat. In the first study, 2.5 mg/kg diazepam was administered 20 min prior to 40 min of immobilization stress. Acute diazepam significantly reduced basal levels of extracellular DA and antagonized the stress-induced increase in cortical DA when compared to untreated stressed rats. Acute diazepam did not significantly effect extracellular DOPAC. In the second study, an experimental group of rats was given approximately 2 mg/kg/day diazepam in their drinking water for 3 weeks. This treatment significantly reduced anxiety as assessed by a staircase test for anxiety. Chronic diazepam had no effect on basal levels of cortical DA. However, chronic diazepam treatment also attenuated stress-induced increases in extracellular DA when compared to untreated stressed control rats. Chronic diazepam did not affect stress-induced changes in DOPAC but it did antagonize the effects of stress on HVA. Thus, acute and chronic diazepam treatment can antagonize stress-induced activation of the mesocortical DA system. It is proposed that this effect is produced through an enhancement of GABAergic neurotransmission by diazepam. The role of the dopaminergic system during stress, anxiety, and schizophrenia is discussed.
中脑皮质多巴胺系统被认为在应激反应的病因学中起重要作用。多巴胺（DA）已被证明会在大鼠额叶皮质中因多种应激源而积累。地西泮，一种抗焦虑苯二氮䓬类药物，可逆转应激对皮质DA的影响。我们研究了急性和慢性给予地西泮对束缚应激诱导的大鼠额叶皮质DA系统变化的影响。在第一项研究中，在40分钟束缚应激前20分钟给予2.5mg/kg地西泮。与未处理的应激大鼠相比，急性给予地西泮显著降低了细胞外DA的基础水平，并拮抗了应激诱导的皮质DA增加。急性给予地西泮对细胞外DOPAC没有显著影响。在第二项研究中，一组实验大鼠在其饮用水中给予约2mg/kg/天地西泮，持续3周。通过焦虑阶梯试验评估，这种治疗显著降低了焦虑。慢性给予地西泮对皮质DA的基础水平没有影响。然而，与未处理的应激对照大鼠相比，慢性给予地西泮治疗也减弱了应激诱导的细胞外DA增加。慢性给予地西泮不影响应激诱导的DOPAC变化，但它确实拮抗了应激对HVA的影响。因此，急性和慢性给予地西泮治疗可拮抗应激诱导的中脑皮质DA系统激活。有人提出这种作用是通过地西泮增强GABA能神经传递产生的。文中讨论了多巴胺能系统在应激、焦虑和精神分裂症中的作用。
