Repeated administration of antidepressant drugs affects the levels of mRNA coding for D1 and D2 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 D1 and D2 receptors in the rat brain. Quantitive in situ hybridization with 35S-labelled oligonucleotide probes has been utilised. The level of mRNA coding for dopamine D1 receptor (D1 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 D1 mRNA in the striatum and in the core region of nucleus accumbens. A similar tendency, i.e.: an increase in the level of D1 mRNA was observed after repeated administration of (+)-oxaprotiline, a selective inhibitor of noradrenaline reuptake. The level of mRNA coding for dopamine D2 receptors (D2 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 D2 mRNA. The results obtained in this study indicate that the levels of mRNA coding for dopamine D1 and D2 receptors are regulated by the antidepressant drugs. The changes concerning the dopamine D2 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.
Dziedzicka-Wasylewska
M
M
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Rogoz
R
R
Klimek
V
V
Maj
J
J
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D015283:Citalopram / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D008376:Maprotiline / Q000031:analogs & derivatives / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D015283:Citalopram; D007099:Imipramine; D008376:Maprotiline; D009638:Norepinephrine; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017367:Selective Serotonin Reuptake Inhibitors; C027299:hydroxymaprotilin