Effects of the sigma receptor ligand SR 31742A on neurotensin biosynthesis in rat basal ganglia

Abstract

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.