Ervin G N, Nemeroff C B
Laboratory of Psychoneuroendocrinology, Duke University Medical Center, Durham, North Carolina 27710.
Neuropsychopharmacology. 1988 Sep;1(3):243-50. doi: 10.1016/0893-133x(88)90024-3.
A number of studies have shown that intracisternal, intracerebroventricular, or direct administration of neurotensin (NT) into the nucleus accumbens (ACC) can antagonize the arousal and excitement produced by activation of the mesolimbic dopamine (DA) system of rats. This study investigated where NT acts relative to DA neurons to exert this antagonistic effect. In this study we selectively removed the majority of limbic forebrain DA terminals by bilateral administration of 6-hydroxydopamine (6-OHDA) into the anterolateral hypothalamus of desipramine-pretreated rats. The 6-OHDA-treated rats subsequently developed DA receptor supersensitivity, as evidenced by behavioral supersensitivity to L-DOPA. The L-DOPA dose employed was subthreshold for behavioral excitation in control rats. The behavioral excitation to L-DOPA in 6-OHDA-treated rats consisted of increases in sniffing and increases in locomotion and/or rearing, along with decreases in resting and sleep. Following bilateral intra-ACC injections of NT, L-DOPA-induced sniffing, rearing, and locomotion decreased significantly, and resting and sleep increased significantly. These data suggest that intra-ACC NT, acting in or proximal to the ACC, can antagonize the behavioral effects of limbic DA stimulation and that this antagonism is postsynaptic to DA neurons.
多项研究表明，向大鼠伏隔核（ACC）脑池内、脑室内注射神经降压素（NT）或直接给药，可拮抗大鼠中脑边缘多巴胺（DA）系统激活所产生的觉醒和兴奋。本研究调查了NT相对于DA神经元发挥这种拮抗作用的位点。在本研究中，我们通过向经去甲丙咪嗪预处理的大鼠双侧下丘脑前外侧注射6-羟基多巴胺（6-OHDA），选择性地去除了大部分边缘前脑DA终末。6-OHDA处理的大鼠随后出现了DA受体超敏反应，对左旋多巴（L-DOPA）的行为超敏反应证明了这一点。所使用的L-DOPA剂量低于对照大鼠行为兴奋的阈值。6-OHDA处理的大鼠对L-DOPA的行为兴奋表现为嗅探增加、运动和/或竖毛增加，同时静息和睡眠减少。双侧ACC内注射NT后，L-DOPA诱导的嗅探、竖毛和运动显著减少，静息和睡眠显著增加。这些数据表明，ACC内的NT作用于ACC内或其附近，可拮抗边缘DA刺激的行为效应，且这种拮抗作用发生在DA神经元的突触后。
