Differential development of autoreceptor subsensitivity and enhanced dopamine release during amphetamine sensitization.
Differential development of autoreceptor subsensitivity and enhanced dopamine release during amphetamine sensitization.
复制标题
DOI：
--
复制
发表时间：
1993
期刊：
影响因子：
--
通讯作者：
M. Wolf;F. J. White;R. Nassar;R. J. Brooderson;M. Khansa
中科院分区：
文献类型：
--
作者：
M. Wolf;F. J. White;R. Nassar;R. J. Brooderson;M. Khansa
多巴胺神经元功能的各种变化被认为是对d-苯丙胺运动刺激作用的行为敏化发展的基础。本研究检查了两种这样的机制的相对重要性后，短期（3-4天）和长期（10-14天）停药从重复安非他明或盐水注射（1毫克/公斤/天，第1-5和8-12天）。首先，单单位记录被用来检查位于大鼠腹侧被盖区中脑多巴胺神经元上的冲动调节体树突自受体的敏感性。其次，在体内微透析被用来检查安非他明的挑战，以增加细胞外多巴胺水平在大鼠延髓核的能力。与盐水处理的大鼠相比，安非他明处理的大鼠在两个时间点都表现出强大的行为敏化。在3至4天的休息时间，在安非他明治疗的大鼠腹侧被盖区观察到自身受体亚敏感性，但安非他明增加丘脑核细胞外多巴胺水平的能力没有显着变化。然而，10至14天后，不再观察到自身受体亚敏感性，但安非他明的挑战导致安非他明治疗的大鼠相比，盐水治疗的细胞外多巴胺水平的显着更大的增加。这些研究结果表明，自身受体亚敏感性是一个短暂的影响，这可能与发展的敏化，而安非他明刺激的多巴胺释放的增强并不伴随早期阶段的行为敏化，但可能参与持久的现象后，较长的停药期。
Various changes in the function of dopamine neurons have been proposed to underly the development of behavioral sensitization to the locomotor stimulant effects of d-amphetamine. The present study examined the relative importance of two such mechanisms after both short (3-4 days off) and longer (10-14 days off) withdrawals from repeated amphetamine or saline injection (1 mg/kg/day, days 1-5 and 8-12). First, single-unit recording was used to examine the sensitivity of impulse-regulating somatodendritic autoreceptors located on mesoaccumbens dopamine neurons in the rat ventral tegmental area. Second, in vivo microdialysis was used to examine the ability of amphetamine challenge to increase extracellular dopamine levels in the rat nucleus accumbens. Amphetamine-treated rats exhibited robust behavioral sensitization at both time points as compared to saline-treated rats. At 3 to 4 days off, autoreceptor subsensitivity was observed in the ventral tegmental area of amphetamine-treated rats, but there was no significant change in the ability of amphetamine to increase extracellular dopamine levels in nucleus accumbens. However, after 10 to 14 days off, autoreceptor subsensitivity was no longer observed, but amphetamine challenge resulted in a significantly greater increase in extracellular dopamine levels in amphetamine-treated as compared to saline-treated rats. These findings suggest that autoreceptor subsensitivity is a transient effect which may be related to the development of sensitization, whereas enhancement of amphetamine-stimulated dopamine release does not accompany early stages of behavioral sensitization, but may be involved in the persistence of the phenomenon after longer withdrawal periods.