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 D4 receptor (D4R) agonist PD168,077 induces a down-regulation of the μ 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/ΔFosB 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/ΔFosB 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.

► Impact of dopamine D4/μ opioid receptor interaction in drug addiction. ► Role of dopamine D4 receptors in the brain. ► Understanding of opioid drug addiction mechanisms.