Nemeroff C B, Kilts C D, Levant B, Bissette G, Campbell A, Baldessarini R J
Department of Psychiatry, Duke University Medical Center, Durham, NC 27710.
Neuropsychopharmacology. 1991 Jan;4(1):27-33.
Rats were treated for 10 days with haloperidol (0.2 or 3 mg/kg/day intraperitoneally [IP]), with either S(+) or R(-) N-n-propylnorapomorphine (NPA; 3 mg/kg IP three times daily) or saline as a placebo control. Brain was microdissected into 11 regions for radioimmunoassay of neurotensin (NT)-like activity under coded ("blind") conditions. Concentrations of NT in rat brain regions ranked central amygdaloid nucleus greater than ventral bed nucleus greater than ventral tegmentum greater than dorsal bed nucleus greater than arcuate nucleus greater than substantia nigra greater than nucleus accumbens septi (accumbens) greater than piriform cortex greater than nucleus caudatus (caudate) greater than mesoprefrontal cortex greater than cingulate cortex, similar to previous observations. Since untreated and placebo-injected control results were indistinguishable, a stress artifact is unlikely to account for the findings. Haloperidol at the lower dose produced no significant changes but, at the higher dose, yielded relatively large (42%-143%) increases of NT concentrations in accumbens, caudate, and substantia nigra. S(+)NPA, which has some properties as a limbic-selective dopamine antagonist, yielded smaller (55%-66%) but significant average increases of NT in accumbens and piriform cortex, and lesser trends toward increases (40%-51%) in caudate, nigra, and mesoprefrontal cortex--all persisting for 5 days after treatment, whereas the R(-) enantiomer, a potent dopaminergic agonist, increased NT only in nigra (by 112%). These observations confirm previous results with haloperidol and add to the impression that S(+)-NPA shares some properties of atypical antipsychotic agents.
将大鼠用氟哌啶醇（0.2或3毫克/千克/天，腹腔注射[IP]）治疗10天，同时分别给予S(+)或R(-)N-正丙基去甲阿朴吗啡（NPA；3毫克/千克，腹腔注射，每日三次）或生理盐水作为安慰剂对照。在编码（“盲法”）条件下，将大脑显微切割成11个区域，用于放射免疫测定神经降压素（NT）样活性。大鼠脑区中NT的浓度排序为：中央杏仁核＞腹侧终纹床核＞腹侧被盖区＞背侧终纹床核＞弓状核＞黑质＞伏隔核＞梨状皮质＞尾状核＞中前额叶皮质＞扣带回皮质，这与之前的观察结果相似。由于未治疗组和注射安慰剂组的对照结果无差异，因此应激假象不太可能解释这些发现。较低剂量的氟哌啶醇未产生显著变化，但较高剂量时，伏隔核、尾状核和黑质中的NT浓度相对大幅增加（42%-143%）。具有一些边缘系统选择性多巴胺拮抗剂特性的S(+)NPA，使伏隔核和梨状皮质中的NT平均增加幅度较小（55%-66%）但具有统计学意义，在尾状核、黑质和中前额叶皮质中增加趋势较小（40%-51%）——所有这些在治疗后持续5天，而R(-)对映体作为一种强效多巴胺能激动剂，仅使黑质中的NT增加（112%）。这些观察结果证实了之前关于氟哌啶醇的结果，并进一步加深了这样的印象，即S(+)-NPA具有一些非典型抗精神病药物的特性。
