Levant B, Nemeroff C B
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina.
J Pharmacol Exp Ther. 1990 Jul;254(1):330-5.
Acute and chronic treatment with antipsychotic drugs, such as haloperidol, selectively increases the concentrations of neurotensin (NT) in the nucleus accumbens and caudate of the rat. These increases in NT concentration in the nucleus accumbens and caudate have been hypothesized to underlie the therapeutic and extrapyramidal effects of antipsychotic drugs, respectively. The present study evaluates the effects of the putative antipsychotic and selective sigma receptor "antagonist" BMY 14802 on regional brain NT concentrations. NT concentrations in discrete brain regions of adult, male, Sprague-Dawley rats were measured by a sensitive and specific radioimmunoassay. Like haloperidol (1 mg/kg i.p.), acute and chronic treatment with BMY 14802 (35 mg/kg/day i.p.) produced significant increases in the concentrations of NT in the nucleus accumbens and anterior and posterior caudate. This effect was dose-dependent. Maximal increases in NT concentration were observed 18 hr after a single dose of BMY 14802. Neither acute nor chronic treatment with the sigma "agonist" (+)-SKF 10,047 (20 mg/kg i.p.), the N-methyl-D-aspartate-phencyclidine binding site antagonist MK-801 (0.25 mg/kg i.p.) or the selective D2 antagonist sulpiride (100 mg/kg i.p.), produced the pattern of NT alterations observed after the administration of BMY 14802. These findings suggest that the blockade of sigma receptors modulates NT concentrations in these brain regions.
使用抗精神病药物（如氟哌啶醇）进行急性和慢性治疗，可选择性增加大鼠伏隔核和尾状核中神经降压素（NT）的浓度。伏隔核和尾状核中NT浓度的增加分别被认为是抗精神病药物治疗作用和锥体外系效应的基础。本研究评估了假定的抗精神病药物和选择性σ受体“拮抗剂”BMY 14802对脑区NT浓度的影响。通过灵敏且特异的放射免疫分析法测量成年雄性Sprague-Dawley大鼠离散脑区的NT浓度。与氟哌啶醇（腹腔注射1mg/kg）一样，BMY 14802（腹腔注射35mg/kg/天）进行急性和慢性治疗后，伏隔核以及尾状核前部和后部的NT浓度显著增加。这种效应呈剂量依赖性。单次注射BMY 14802后18小时观察到NT浓度最大增加。σ“激动剂”（+）-SKF 10,047（腹腔注射20mg/kg）、N-甲基-D-天冬氨酸-苯环利定结合位点拮抗剂MK-801（腹腔注射0.25mg/kg）或选择性D2拮抗剂舒必利（腹腔注射100mg/kg）的急性或慢性治疗均未产生BMY 14802给药后观察到的NT改变模式。这些发现表明，σ受体的阻断调节了这些脑区的NT浓度。
