REPEATED ADMINISTRATION OF ANTIDEPRESSANT DRUGS AFFECTS THE LEVELS OFMESSENGER-RNA CODING FOR D-1 AND D-2 DOPAMINE-RECEPTORS IN THE RAT-BRAIN

The present study examined the effects of acute and repeated administr ation of three antidepressant drugs (imipramine, citalopram and (+)-ox aprotiline) on the levels of mRNA coding for dopamine D-1 and D-2 rece ptors in the rat brain. Quantitive in situ hybridization with S-35-lab elled oligonucleotide probes has been utilised. The level of mRNA codi ng for dopamine D-1 receptor (D-1 mRNA) is decreased following repeate d administration of imipramine, both in the nucleus accumbens and in t he striatum. On the other hand, the repeated administration of citalop ram, the selective inhibitor of serotonin reuptake, resulted in an inc rease 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 lev el of D-1 mRNA was observed after repeated administration of (+)-oxapr otiline, a selective inhibitor of noradrenaline reuptake. The level of mRNA coding for dopamine D-2 receptors (D-2 mRNA) was increased in al l the brain regions studied, both after administration of imipramine a nd citalopram. (+)-Oxaprotiline did not produce any statistically sign ificant 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 con cerning the dopamine D-2 receptors are more consistent and fit in with the previously described binding and behavioral effects and seem to b e important for the mechanism of action of antidepressant drugs.