THE EFFECT OF PROLONGED TREATMENT WITH IMIPRAMINE ON THE BIOSYNTHESISAND FUNCTIONAL-CHARACTERISTICS OF D-2 DOPAMINE-RECEPTORS IN THE RAT CAUDATE-PUTAMEN

1 The present study shows the effects of imipramine in a single dose ( 10 mg kg(-1), p.o.) or following repeated (14 days, twice a day) treat ment on the level of mRNA coding for D-2 dopamine receptors in the rat caudate putamen (CP). Repeated administration of imipramine resulted in the increase of the level of mRNA coding for D-2 dopamine receptors . 2 Radioligand binding studies with the D-2 receptor agonist, [H-3]-N -0437, indicated, that following imipramine administration, the affini ty of the agonist for the D-2 dopamine receptor significantly increase d, though without any alterations in the B-Max. 3 Pharmacological mani pulations (by use of forskolin, GppNHp and quinpirole) of the cyclic A MP generating system, ex vivo following administration of imipramine i ndicated that an up-regulation of factors inhibiting cyclic GMP format ion takes place. 4 Most probably it is the D-2 dopamine receptor which undergoes functional up-regulation, resulting from the enhancement of its biosynthesis.