NEUROTENSIN INJECTED INTO THE NUCLEUS-ACCUMBENS BLOCKS THE PSYCHOSTIMULANT EFFECTS OF COCAINE BUT DOES NOT ATTENUATE COCAINE SELF-ADMINISTRATION IN THE RAT
NEUROTENSIN INJECTED INTO THE NUCLEUS-ACCUMBENS BLOCKS THE PSYCHOSTIMULANT EFFECTS OF COCAINE BUT DOES NOT ATTENUATE COCAINE SELF-ADMINISTRATION IN THE RAT
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DOI：
10.1016/0006-8993(93)90808-z
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发表时间：
1993-09-17
期刊：
影响因子：
2.9
通讯作者：
KOOB, GF
中科院分区：
文献类型：
--
作者：
ROBLEDO, P;MALDONADO, R;KOOB, GF
神经肽神经降压素(NT)已被证明调节中脑边缘多巴胺能活动。神经降压素注射到VTA产生运动刺激和伏隔核多巴胺的释放。相比之下，当神经降压素被注入伏隔核时，它会产生类似神经镇静剂的作用，比如减弱由精神刺激剂引起的运动活动。在本研究中，伏隔核内注射神经降压素可能调节可卡因的精神刺激和强化作用的假说得到了验证。在实验一中，训练大鼠按照FR5强化计划自我静脉注射可卡因。在建立基线反应后，在大鼠的伏隔核内植入双侧套管。一周后，大鼠在自我给药前立即向伏隔核内注射不同剂量的神经降压素(4.2、8.4和16.7杯，总剂量为双侧)。测试的任何剂量的神经降压素对可卡因的自我给药都没有明显的影响。但在实验2中，伏隔核内注射4.2和16.7mug的神经降压素可显著降低急性注射可卡因(15 mg/kg，i.p)引起的运动兴奋。16.7µg可减弱安非他明(0.75 mg/kg ip)对小鼠的运动兴奋作用。因此，伏核中的神经降压素似乎特异性地调节可卡因的急性运动激活特性，但不能调节可卡因的自我给药。NT与伏隔核多巴胺相互作用的不同机制可能提供了一种有选择地改变精神刺激运动行为的方法，而不影响精神刺激强化。
The neuropeptide neurotensin (NT) has been shown to modulate mesolimbic dopaminergic activity. Neurotensin injected into the VTA produces motor stimulation and release of dopamine in the nucleus accumbens. In contrast, when neurotensin is administered into the nucleus accumbens, it produces neuroleptic-like effects such as attenuation of the locomotor activity elicited by psychostimulants. In the present study, the hypothesis that neurotensin injected into the nucleus accumbens might modulate the psychostimulant and reinforcing actions of cocaine was tested. In experiment one, rats were trained to self-administer cocaine intravenously on an FR5 schedule of reinforcement. Following the establishment of baseline responding, rats were implanted with bilateral cannulae in the nucleus accumbens. One week later, rats were injected into the nucleus accumbens with various doses of neurotensin (4.2, 8.4 and 16.7 mug, total doses bilaterally) immediately prior to the self-administration session. No significant effects were found with any of the doses of neurotensin tested on the self-administration of cocaine. However, in experiment 2, neurotensin at doses of 4.2 and 16.7 mug injected into the nucleus accumbens significantly reduced the locomotor activation induced by an acute injection of cocaine (15 mg/kg i.p.) and a dose of 16.7 mug attenuated the locomotor activation induced by amphetamine (0.75 mg/kg i.p.). Thus, neurotensin in the nucleus accumbens appears to specifically modulate the acute locomotor activating properties of cocaine but not cocaine self-administration. Different mechanisms by which NT interacts with dopamine in the nucleus accumbens may provide a means of selectively altering psychostimulant motor actions without affecting psychostimulant reinforcement.