The effect of prolonged treatment with imipramine on the biosynthesis and functional characteristics of D₂ dopamine receptors in the rat caudate putamen

Abstract

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 D₂ dopamine receptors in the rat caudate putamen (CP). Repeated administration of imipramine resulted in the increase of the level of mRNA coding for D₂ dopamine receptors.

2. Radioligand binding studies with the D₂ receptor agonist, [³H]-N-0437, indicated, that following imipramine administration, the affinity of the agonist for the D₂ 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 D₂ dopamine receptor which undergoes functional up-regulation, resulting from the enhancement of its biosynthesis.

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