THE EFFECT OF IMIPRAMINE ON THE AMOUNT OF MESSENGER-RNA CODING FOR RAT DOPAMINE D-2 AUTORECEPTORS

Several reports have investigated the possibility that chronic antidep ressant treatment alters dopamine autoreceptors. Since radioligand bin ding studies do not differentiate between presynaptic and postsynaptic dopamine D-2 receptors in the rat forebrain, we used the in situ hybr idization technique to measure the amount of mRNA coding for dopamine D-2 autoreceptors in the dopaminergic cell bodies. The amount of mRNA coding for dopamine D-2 autoreceptors in the rat mesencephalon was ana lyzed following acute and repeated treatment with imipramine. the most widely used antidepressant drug. No significant changes in the amount of mRNA were observed in the substantia nigra of the rat, after acute or repeated treatment with imipramine. In the ventral tegmental area repeated treatment with imipramine (14 days, twice a day) increased th e amount of dopamine D-2 autoreceptor mRNA in the lateral part of this brain region (containing nucleus paranigralis and n. parabrachialis p igmentosus), without there being any significant changes in the more m edial part (n. interfascicularis and n. linearis). The increase in the amount of dopamine D-2 autoreceptor mRNA in the ventral tegmental are a started to be significant 72 h after acute imipramine. Moreover, thi s increase was also observed after 14 drug-free days following the acu te administration of the drug. The results indicate the different sens itivity of neurons synthesizing dopamine autoreceptors for imipramine. Another interesting finding is the observation that acute treatment w ith imipramine seems to be sufficient to trigger changes as a function of time regardless of whether imipramine is again administered, provi ding a possible explanation for the delayed therapeutic effect of the drug. (C) 1997 Elsevier Science B.V.