D-4 and D-1/D-5 dopamine receptors interact synergistically in the rat striatum

D1-like (D-1 and D-5) and D-2-like (D-2, D-3 and D-4) dopamine receptor sub types interact synergistically in many paradigms, such as dopamine (DA) ago nist-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 D- 4 receptor in D1/D2 interactions by examining the effects of the D-1/D-5 ag onist SKF 38393 and the D-4 agonist PID 168,077 on the expression of c-Fos in rats with unilateral 6-Hydroxydopamine(6-OHDA) lesions of the nigroestri atal pathway. Systemic administration of PD 168,077 led to a higher dose-de pendent induction of c-Fos in the lesioned striatum as compared with the co ntralateral portion. In all cases, c-Fos expression pattern was heterogeneo us, being more abundant in the medial part. A low dose of SKF 38393 or PID 168,077 alone produce little induction of c-Fos, but combination of both ag onists produced a synergistic effect on c-Fos expression. In this case c-Fo s-positive nuclei pattern was heterogeneous in the latero-medial axis and o ccurred primarily in patches. Furthermore, we have demonstrated that activa ted cells are medium-sized projecting neurons. This finding suggest that D- 4 dopamine receptors play an important role in D1/D2 interactions occurred in an animal model of Parkinson's disease.