Morrow B A, Roth R H
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520-8066, USA.
Synapse. 1996 Jul;23(3):174-81. doi: 10.1002/(SICI)1098-2396(199607)23:3<174::AID-SYN6>3.0.CO;2-5.
The aim of this study was to examine the effects of serotonergic lesions to the dorsal raphe on midbrain dopaminergic systems. 5,7-Dihydroxytryptamine lesions of the dorsal raphe resulted in a substantial loss of serotonin in the medial prefrontal cortex (about 75%) and the nucleus accumbens (about 50%), while no change in DA levels or DA metabolism were noted in either region at 12 days postlesion. A transient basal locomotor activation was noted in the lesioned animals compared to the sham controls 7 to 12 days after the lesions. The locomotor response to an acute dose of cocaine was also enhanced in 5,7-dihydroxytryptamine lesioned rats, however, no change in the time course or magnitude of the behavioral locomotor response to repeated cocaine administration was observed. Restraint for 30 min increased DA metabolism in both the NAS and mPFC of sham rats, as expected. However, in 5,7-dihydroxytryptamine lesioned rats, restraint stress enhanced the usual stress-induced increase in DA metabolism by about 50 and 150% in the medial prefrontal cortex and nucleus accumbens, respectively. Our results indicate the 5,7-dihydroxytryptamine lesions of the dorsal raphe lower serotonin in both the mPFC and NAS leading to an enhanced responsiveness of the DA projections in both regions. This effect may be explained by a loss of sensitivity of DA receptors in 5,7-dihydroxytryptamine denervated rats. This interpretation implies that the stimulated, but not basal, release of DA in the mPFC and NAS is dependent on serotonin tone.
本研究的目的是检验中缝背核的5-羟色胺能损伤对中脑多巴胺能系统的影响。中缝背核的5,7-二羟基色胺损伤导致内侧前额叶皮质（约75%）和伏隔核（约50%）中的5-羟色胺大量丧失，而在损伤后12天，这两个区域的多巴胺水平或多巴胺代谢均未发现变化。与假手术对照组相比，损伤后7至12天，损伤动物出现短暂的基础运动激活。5,7-二羟基色胺损伤的大鼠对急性剂量可卡因的运动反应也增强了，然而，对重复给予可卡因的行为运动反应的时间进程或幅度未观察到变化。如预期的那样，对假手术大鼠约束30分钟会增加伏隔核和内侧前额叶皮质中的多巴胺代谢。然而，在5,7-二羟基色胺损伤的大鼠中，约束应激分别使内侧前额叶皮质和伏隔核中通常由应激诱导的多巴胺代谢增加约50%和150%。我们的结果表明，中缝背核的5,7-二羟基色胺损伤降低了内侧前额叶皮质和伏隔核中的5-羟色胺水平，导致这两个区域的多巴胺投射反应性增强。这种效应可能是由于5,7-二羟基色胺去神经支配大鼠中多巴胺受体敏感性丧失所致。这一解释意味着，内侧前额叶皮质和伏隔核中多巴胺的刺激释放而非基础释放依赖于5-羟色胺张力。
