The effects and mechanisms of locally applied d-amphetamine (AMPH) into the ventral tegmental area (VTA) on extracellular dopamine (DA) concentrations in both the nucleus accumbens (N ACC) and the medial prefrontal cortex (mPFC) were investigated. A solution containing either, 0, 100, 500 or 1000 microM AMPH was infused, using a 1-ml Hamilton syringe, into the VTA of chloral hydrate-anesthetized rats for 100 min through a microdialysis probe. Infusion of AMPH into the VTA dose-dependently increased extracellular DA in the N ACC and in the mPFC. The introductory rate of AMPH application through the dialysis probe into the VTA was estimated simultaneously. Local infusion of either a selective alpha adrenoceptor antagonist (phentolamine, 1 and 10 microM) or a selective beta adrenoceptor antagonist (alprenolol, 1 and 10 nM) dose-dependently blunted the intra-VTA AMPH-induced extracellular DA increase in the N ACC. Further, local infusion of phentolamine (0.1 and 1 microM) and alprenolol (1 and 10 nM) appreciably and dose-dependently reduced the effects of AMPH on the DA increase in the mPFC. These results suggest that intra-VTA AMPH can enhance DA release in the N ACC and in the mPFC by activating noradrenergic neurotransmission in the VTA.