Effect of acute and continuous morphine treatment on transcription factor expression in subregions of the rat caudate putamen. Marked modulation by D4 receptor activation

Acute administration of the dopamine D-4 receptor (D4R) agonist PD168,077 induces a down-regulation of the mu opioid receptor (MOR) in the striosomal compartment of the rat caudate putamen (CPu), suggesting a striosomal D4R/MOR receptor interaction in line with their high co-distribution in this brain subregion. The present work was designed to explore if a D4R/MOR receptor interaction also occurs in the modulation of the expression pattern of several transcription factors in striatal subregions that play a central role in drug addiction. Thus, c-Fos, FosB/Delta FosB and P-CREB immunoreactive profiles were quantified in the rat CPu after either acute or continuous (6-day) administration of morphine and/or PD168,077. Acute and continuous administration of morphine induced different patterns of expression of these transcription factors, effects that were time-course and region dependent and fully blocked by PD168,077 co-administration. Moreover, this effect of the D4R agonist was counteracted by the D4R antagonist L745,870. Interestingly, at some time-points, combined treatment with morphine and PD168,077 substantially increased c-Fos, FosB/Delta FosB and P-CREB expression. The results of this study give indications for a general antagonistic D4R/MOR receptor interaction at the level of transcription factors. The change in the transcription factor expression by D4R/MOR interactions in turn suggests a modulation of neuronal activity in the CPu that could be of relevance for drug addiction. (C) 2011 Elsevier B.V. All rights reserved.