Bastianetto S, Rouquier L, Perrault G, Sanger D J
Synthelabo Recherche, Bagneux, France.
Neuropharmacology. 1995 Mar;34(3):281-7. doi: 10.1016/0028-3908(94)00156-m.
The distribution of sigma sites in brain areas enriched in dopamine, and the finding that circling behaviour can be elicited by specific sigma ligands such as DTG (di-o-tolylguanidine) suggest a modulatory role of these sites in the dopaminergic system. The present study was carried out to investigate further this hypothesis. Circling behaviour induced in rats by unilateral intranigral injection of DTG (10 nmol/rat) was decreased by haloperidol (0.1 mg/kg, i.p.), clebopride (0.25 mg/kg, i.p.) and SCH 23390 (0.03 mg/kg, s.c.) indicating that an interaction between sigma sites and the midbrain dopaminergic system may be involved in this rotational behaviour. Microdialysis experiments in freely moving rats showed that unilateral intranigral injection of DTG (5, 10, 20 nmol/rat) produced increases in extracellular levels of dopamine metabolites (DOPAC, HVA) in the ipsilateral striatum which correlated with the number of rotations. In addition intranigral injection of DTG (10 nmol/rat) produced increases in tissular dopamine metabolite levels in the ipsilateral striatum without affecting dopamine metabolite levels in limbic structures. These results indicate that sigma sites may be involved in the modulation of the dopaminergic motor system.
σ位点在富含多巴胺的脑区中的分布，以及特定的σ配体如DTG（二邻甲苯基胍）可引发转圈行为这一发现，提示了这些位点在多巴胺能系统中的调节作用。本研究旨在进一步探究这一假说。单侧黑质内注射DTG（10 nmol/只大鼠）诱导的大鼠转圈行为，可被氟哌啶醇（0.1 mg/kg，腹腔注射）、氯波必利（0.25 mg/kg，腹腔注射）和SCH 23390（0.03 mg/kg，皮下注射）所降低，这表明σ位点与中脑多巴胺能系统之间的相互作用可能参与了这种旋转行为。对自由活动大鼠进行的微透析实验表明，单侧黑质内注射DTG（5、10、20 nmol/只大鼠）可使同侧纹状体中多巴胺代谢产物（DOPAC、HVA）的细胞外水平升高，且与旋转次数相关。此外，黑质内注射DTG（10 nmol/只大鼠）可使同侧纹状体中的组织多巴胺代谢产物水平升高，而不影响边缘结构中的多巴胺代谢产物水平。这些结果表明，σ位点可能参与了多巴胺能运动系统的调节。
