In vivo regulation of dopamine and noradrenaline release by alpha2A-adrenoceptors in the mouse nucleus accumbens

The present study investigated the role of alpha2A-adrenoceptor (alpha(2A)-AR) subtype in the regulation of noradrenaline (NA) and dopamine (DA) release in the nucleus accumbens (NAc). The effect of locally infused and systemically injected alpha(2)-AR agonist, dexmedetomidine (DMT), and alpha(2)-AR antagonist, atipamezole, on NA and DA release was investigated in alpha(2A)-AR knockout and control mice by using in vivo microdialysis. In addition, we compared the drug effects on DA and NA release in the NAc to their effect on locomotor activity. Baseline NA and DA concentrations did not differ between genotypes. Local infusion of DMT decreased, in a concentration-dependent manner, NA, but not DA, levels in the control mice. However, systemic injection of DMT decreased both NA and DA levels in the control mice. In both cases DMT had no effects on transmitter release in alpha(2A)-AR knockout mice. Our results suggest that alpha(2)-ARs regulate the release of NA, but not DA, at the terminal level in the NAc. However, alpha(2)-ARs regulate DA release in the NAc indirectly by their effect on DA neurones in the ventral tegmental area via an unknown mechanism. In both cases the regulation is mediated by alpha(2A)-adrenoceptor subtype. Also the modulation of locomotor activity by alpha(2)-AR agonist and antagonist seems to be mediated via alpha(2A)-adrenoceptors.