Extracellular levels of dopamine (DA), serotonin (5-HT), and norepinephrine (NE) were measured by microdialysis in conscious rats equipped with dual probes, one in the ventral tegmental area (VTA) and another one in the contralateral nucleus accumbens (NACC). Dialysate content of all amines in both regions was essentially abolished by local infusion of tetrodotoxin (1 microM) or Ca2+-free buffer. Injection of the selective DA uptake blocker GBR 12935 (15 mg/kg i.p.) increased DA, as well as NE and, to a lesser extent, 5-HT in the VTA; it increased DA more than 5-HT in the NACC. The selective NE uptake blocker desipramine (10 mg/kg i.p.) increased NE but also 5-HT in the VTA and NACC; the DA level was persistently enhanced in the VTA, whereas in the NACC it initially rose and then fell below baseline value. The selective 5-HT uptake blocker citalopram (15 mg/kg i.p.) was generally more effective in elevating dialysate level of 5-HT than that of other amines in both regions. Cocaine (20 mg/kg i.p.) was non-selective in enhancing all three amines in both regions. There is considerable crosstalk between monoamine systems occurring upon systemic administration of uptake blockers, and the VTA and NACC are notably different in the time course of the DA effect (long-lasting versus transient).