Short Report D4 and D1/D5 dopamine receptors interact synergistically in the rat striatum

*Address correspondence to: Sonia Trías. Department of Cell Biology, University of Málaga, 29071 Málaga, Spain. e-mail: [email protected] ABSTRACT D1-like (D1 and D5) and D2-like (D2, D3 and D4) dopamine receptor subtypes interact synergistically in many paradigms, such as dopamine (DA) agonist-stimulated motor behaviour and striatal c-Fos expression in intact and DA-depleted striatum. However, it is not clear which subtypes of dopamine receptor are involved in these process. We now report the implication of D4 receptor in D1/D2 interactions by examining the effects of the D1/D5 agonist SKF 38393 and the D4 agonist PD 168,077 on the expression of c-Fos in rats with unilateral 6-Hydroxydopamine (6-OHDA) lesions of the nigroestriatal pathway. Systemic administration of PD 168,077 led to a higher dose-dependent induction of c-Fos in the lesioned striatum as compared with the contralateral portion. In all cases, cFos expression pattern was heterogeneous, being more abundant in the medial part. A low dose of SKF 38393 or PD 168,077 alone produce little induction of c-Fos, but combination of both agonists produced a synergistic effect on c-Fos expression. In this case c-Fospositive nuclei pattern was heterogeneous in the latero-medial axis and occurred primarily in patches. Furthermore, we have demonstrated that activated cells are medium-sized projecting neurons. This finding suggest that D4 dopamine receptors play an important role in D1/D2 interactions occurred in an animal model of Parkinson’s disease.