The role of dopamine D2 receptor in the behavioral effects of imipramine--study with the use of antisense oligonucleotides.
Antisense strategies have a potential to specifically block the production of a given protein, e.g. receptor subtype, thus may help to uncover its behavioral and/or biochemical function. In the present study we demonstrated the utility of this approach for studying the role of dopamine D2 receptors in the anti-immobility effect of imipramine in the forced swimming test. Following intracerebroventricular (i.c.v.) administration of phosphorothioate oligonucleotide complementary to mRNA encoding for dopamine D2 receptors (D2 antisense ODN; 1 nmol/1 microl H2O, twice a day for 5 days) to the rats, the decrease in the locomotor activity (shortened total distance travelled and decrease in vertical activity, without differences in the stereotypic movements of animals), as well as the decrease of specific binding of [3H]raclopride in the striatum and limbic forebrain were observed. At the same time, i.c.v. administration of D2 antisense ODN reversed the effect of imipramine in the forced swimming test, what may indicate that the dopamine D2 receptors play a significant role in the behavioral anti-immobility effects of imipramine.
Dziedzicka-Wasylewska
M
M
Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Kolasiewicz
W
W
Rogóz
Z
Z
Margas
W
W
Maj
J
J
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology; D007099:Imipramine / Q000494:pharmacology*; D007103:Immobilization / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D020891:Raclopride / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000502:physiology
D000929:Antidepressive Agents, Tricyclic; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D020891:Raclopride; D007099:Imipramine