Nerve growth factor-inducible B is a closely related member of the steroid-thyroid hormone receptor family of ligand-activated transcription factor. Recent evidence suggests a close relationship between nerve growth factor-inducible B and the dopamine system. Basal expression of messenger RNA for nerve growth factor-inducible B is relatively high in the striatum. The aims of the present study were: (i) to study the basal distribution and the modulation of striatal nerve growth factor-inducible B messenger RNA expression by dopamine and serotonin agonists, and (ii) to investigate the effects of combined administration of dopamine (D) and serotonin (5-HT) agonists. First, we investigated the effects of SKF38393 (D1), quinpirole (D2), 8-hydroxy-2-(di-n-propylaminotetralin) (5-HT1A) and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (5-HT2A/2C) administered alone on striatal nerve growth factor-inducible B messenger RNA expression. In a second series of experiments, the effects of a combined administration of dopamine D1 and serotonin 5-HT1A or 5-HT2A/2C agonists were studied. The goal of the last series of experiments was to determine the effects of a combined administration of the dopamine D2 agonist and either serotonin 5-HT1A or 5-HT2A/2C agonists. Our results show that: (i) striatal nerve growth factor-inducible B messenger RNA expression exhibited a lateral-medial gradient in drug-naive rats, (ii) quinpirole and 8-hydroxy-2-(di-n-propylaminotetralin) administered alone induced a significant decrease in striatal nerve growth factor-inducible B messenger RNA expression while 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane significantly increased it, (iii) complex interactions were found when dopamine D1 and serotonin 5-HT1A or 5-HT2A/2C agonists were administered in combination, and (iv) combined administration of quinpirole and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane resulted in a significant decrease in nerve growth factor-inducible B expression. Taken together, these results demonstrate that striatal nerve growth factor-inducible B messenger RNA expression can be modulated by both dopamine and serotonin agonists. They also point out the existence of complex interactions between dopamine and serotonin in regard to striatal expression of the immediate-early transcription factor nerve growth factor-inducible B.