Neurotensin modulates the binding characteristics of dopamine D₂ receptors in rat striatal membranes also following treatment with toluene

The effects of neurotensin in vitro (1-100 nM) on the binding characteristics of [³H]N-propylnorapomorphine ([³H]NPA) were analysed in striatal membrane preparations of the adult male rat. Subsequently, it was investigated whether the modulatory effects of 10 nM neurotensin on [³H]NPA binding were altered by treatment with toluene in vivo (80 p.p.m., 3 days, 6 h day^-1) and in vitro (19 μmol ml^-1). Displacement of [³H]NPA binding by raclopride (IC₅₀ about 15 nM) and SCH 23390 (without effect) indicated that [³H]NPA labelled only D₂ dopamine receptors in the present study. Neurotensin was found to reduce the affinity of D₂ receptors with a maximum response at 10 nM. At this concentration the K(D) value was increased by 30-40% without any consistent changes in the number of binding sites. The modulatory effect of neurotensin remained intact also following toluene treatment in vivo and in vitro, although at a higher K(D) range, since toluene alone increased the K(D) value of [³H]NPA binding by 40-50%. Thus, the mechanisms mediating the effects of neurotensin and toluene on the D₂ receptor are likely to be different. When neurotensin and toluene treatments were combined, the K(D) values of [³H]NPA binding were about twice as high as in non-treated controls. These additive effects may lead to a severely decreased efficiency of dopamine D₂-mediated neurotransmission in vivo.