The effect of imipramine on the amount of mRNA coding for rat dopamine D2 autoreceptors

Several reports have investigated the possibility that chronic antidepressant treatment alters dopamine autoreceptors. Since radioligand binding studies do not differentiate between presynaptic and postsynaptic dopamine D2 receptors in the rat forebrain, we used the in situ hybridization technique to measure the amount of mRNA coding for dopamine D2 autoreceptors in the dopaminergic cell bodies. The amount of mRNA coding for dopamine D2 autoreceptors in the rat mesencephalon was analyzed 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 the amount of dopamine D2 autoreceptor mRNA in the lateral part of this brain region (containing nucleus paranigralis and n. parabrachialis pigmentosus), without there being any significant changes in the more medial part (n. interfascicularis and n. linearis). The increase in the amount of dopamine D2 autoreceptor mRNA in the ventral tegmental area started to be significant 72 h after acute imipramine. Moreover, this increase was also observed after 14 drug-free days following the acute administration of the drug. The results indicate the different sensitivity of neurons synthesizing dopamine autoreceptors for imipramine. Another interesting finding is the observation that acute treatment with imipramine seems to be sufficient to trigger changes as a function of time regardless of whether imipramine is again administered, providing a possible explanation for the delayed therapeutic effect of the drug.