A circadian oscillator located within the retina controls melatonin synthesis in the retina of mammals. In non-mammalian vertebrates retinal melatonin and dopamine appear to act as mutually inhibitory paracrine signals for night and day, respectively; while in mammals this mutually inhibitory capability has now been fully demonstrated. In this study using a flow-through culture apparatus we investigated melatonin release from cultured retinas of golden hamster (Mesocricetus auratus) in the presence of dopamine or dopaminergic agonists and antagonists. Neural retinas were cultured with medium 199 for 24 h in a flow-through apparatus at the temperature 33 degrees C. During the subjective night the culturing medium was supplemented with dopamine, dopamine receptor antagonists or agonists. At the concentration of 0.1 microM dopamine did not inhibit melatonin release, while at higher dopamine concentration (1 to 1000 microM) melatonin release was inhibited in a dose-dependent manner. These effects appeared to be mediated by a D2/D4 receptor, because D2 and D4 receptor agonists (100 microM), but not D1/D5 receptor agonists (100 microM), inhibited melatonin release. Furthermore, D2/D4 selective receptor antagonists (100 microM) in conjunction with 100 microM dopamine blocked melatonin suppression, whereas a D1/D5 selective receptors antagonist was completely ineffective. Taken together, these results directly demonstrate for the first time that in the retina of mammals dopamine may suppress melatonin, and that suppression is mediated by D2/D4 dopaminergic receptors.