The effect of prolonged treatment with imipramine on the biosynthesis and functional characteristics of D2 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) treatment 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 affinity of the agonist for the D-2 dopamine receptor significantly increased, though without any alterations in the B-Max. 3 Pharmacological manipulations (by use of forskolin, GppNHp and quinpirole) of the cyclic AMP generating system, ex vivo following administration of imipramine indicated that an up-regulation of factors inhibiting cyclic GMP formation takes place. 4 Most probably it is the D-2 dopamine receptor which undergoes functional up-regulation, resulting from the enhancement of its biosynthesis.