The efficacy of milnacipran (IxeIR) in the prevention of recurrent depression: Effects on quality of life

A variety of neuroleptics with mixed D2R/D3R antagonist properties, on acute administration, all diminish neurotensin mRNA levels in D3R-expressing neurotensin neurons (in ventromedial shell), whereas they induce opposite effects on D2R-expressing neurotensin neurons (in cone). Recent research confirms that this effect is selectively related to D3R blockade, because it is reproduced by administration of nafadotride in a D3R-selective dosage. In addition, the haloperidol-induced decrease in neurotensin mRNA in ventromedial shell is prevented on coadministration of DO-897, a novel highly selective and partial D3R agonist. D3R and D1R are highly expressed in the islands of Calleja, a structure of poorly defined physiological role, receiving a sparse dopaminergic innervations from the mesencephalon and from which D2R is absent. Double hybridization studies showed D1R and D3R mRNAs to be coexpressed in a high percentage of substance P granule cells, the major neuronal population of the islands. The opposite roles of these two receptor subtypes are shown by studies in which the effects of agonist or antagonist administration were evaluated on the expression of c-fos. Whereas SKF 38393, a D1R agonist, enhances it markedly, quinpirole, a D2R/D3R agonist, has an opposite effect; in addition, endogenous dopamine must have a tonic effect on this system, because c-fos expression is decreased and increased on treatment by SCH 23390 and nafadotride, respectively.