Labie C, Saubusse P, Keane P E, Le Fur G, Soubrié P
Sanofi Recherche, Toulouse, France.
Synapse. 1995 Apr;19(4):241-6. doi: 10.1002/syn.890190403.
The effects of SR 31742A, a specific sigma ligand, were investigated on neurotensin (NT) biosynthesis in the basal ganglia of the rat. Both single and repeated treatments with either SR 31742A (20 mg/kg i.p.) or haloperidol (1 mg/kg i.p.) increased the concentration of NT-like immunoreactivity (NT-li) in the nucleus accumbens. In contrast to haloperidol, the administration of SR 31742A failed to increase the concentration of NT-li in the caudate-putamen. We have further investigated drug-induced variations in NT biosynthesis by studying NT/neuromedin N (NT/NN) mRNA levels in the nucleus accumbens and the ventral tegmental area of the rat following SR 31742A administration. The NT/NN mRNA levels in the ventral tegmental area were increased by a maximum of fifteen fold (7 h at 20 mg/kg i.p.). A lower increase in NT/NN mRNA levels was elicited in the nucleus accumbens. These results suggest that the increase in NT-li observed after SR 31742A treatment, like that produced by haloperidol, may result from an increase of NT biosynthesis. Furthermore, the effects of SR 31742A on NT metabolism are similar to those of atypical antipsychotics, since they appear to be selective for the limbic system.
研究了特异性σ配体SR 31742A对大鼠基底神经节中神经降压素（NT）生物合成的影响。单次或重复给予SR 31742A（腹腔注射20 mg/kg）或氟哌啶醇（腹腔注射1 mg/kg）均能增加伏隔核中NT样免疫反应性（NT-li）的浓度。与氟哌啶醇不同，给予SR 31742A未能增加尾状核-壳核中NT-li的浓度。我们通过研究给予SR 31742A后大鼠伏隔核和腹侧被盖区中NT/神经介素N（NT/NN）mRNA水平，进一步研究了药物诱导的NT生物合成变化。腹侧被盖区中NT/NN mRNA水平最多增加了15倍（腹腔注射20 mg/kg，7小时）。伏隔核中NT/NN mRNA水平的增加幅度较小。这些结果表明，SR 31742A治疗后观察到的NT-li增加，与氟哌啶醇产生的增加一样，可能是由于NT生物合成增加所致。此外，SR 31742A对NT代谢的影响与非典型抗精神病药物相似，因为它们似乎对边缘系统具有选择性。
