Repeated administration of antidepressant drugs affects the levels of mRNA coding for D-1 and D-2 dopamine receptors in the rat brain

The present study examined the effects of acute and repeated administration of three antidepressant drugs (imipramine, citalopram and (+)-oxaprotiline) on the levels of mRNA coding for dopamine D-1 and D-2 receptors in the rat brain. Quantitive in situ hybridization with S-35-labelled oligonucleotide probes has been utilised. The level of mRNA coding for dopamine D-1 receptor (D-1 mRNA) is decreased following repeated administration of imipramine, both in the nucleus accumbens and in the striatum. On the other hand, the repeated administration of citalopram, the selective inhibitor of serotonin reuptake, resulted in an increase in the level of D-1 mRNA in the striatum and in the core region of nucleus accumbens. A similar tendency, i.e.: an increase in the level of D-1 mRNA was observed after repeated administration of (+)-oxaprotiline, a selective inhibitor of noradrenaline reuptake. The level of mRNA coding for dopamine D-2 receptors (D-2 mRNA) was increased in all the brain regions studied, both after administration of imipramine and citalopram. (+)-Oxaprotiline did not produce any statistically significant changes in the level of D-2 mRNA. The results obtained in this study indicate that the levels of mRNA coding for dopamine D-1 and D-2 receptors are regulated by the antidepressant drugs. The changes concerning the dopamine D-2 receptors are more consistent and fit in with the previously described binding and behavioral effects and seem to be important for the mechanism of action of antidepressant drugs.