The role of dopamine D-2 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 beh avioral and/or biochemical function. In the present study we demonstrated t he utility of this approach for studying the role of dopamine D-2 receptors in the anti-immobility effect of imipramme In the forced swimming test. Fo llowing intracerebroventricular (i.c.v.) administration of phosphorothioate oligonucleotide complementary to mRNA encoding for dopamine D-2 receptors (D-2 antisense ODN; 1 nmol/1 mu 1 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 [H-3] raclopride in the striatum and limbic forebrain were observed. At the same time, i.c.v. administration of D-2 antisense ODN reversed the effect of imi pramine in the forced swimming test, what may indicate that the dopamine D- 2 receptors play a significant role in the behavioral anti-immobility effec ts of imipramine.