Locally application of amphetamine into the ventral tegmental area enhances dopamine release in the nucleus accumbens and the medial prefrontal cortex through noradrenergic neurotransmission.

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.