In vivo regulation of dopamine and noradrenaline release by α2A-adrenoceptors in the mouse prefrontal cortex

The present study investigated the role of alpha(2A) -adrenoceptor subtype in the regulation of noradrenaline and dopamine release in the medial prefrontal cortex. The effect of local introduction of the alpha2-adrenoceptor agonist dexmedetomidine (10(-9) -10(-8) m) on noradrenaline and dopamine release was investigated in alpha(2A) -adrenoceptor knockout and control mice by using in vivo microdialysis. Furthermore, to reveal a possible distinction between regulation of baseline and peak release, we sampled the dialysate during both rest and handling-induced mild stress. Baseline noradrenaline and dopamine concentrations did not differ between alpha(2A) -adrenoceptor knockout and control mice. Dexmedetomidine decreased, in a concentration-dependent manner, noradrenaline and dopamine levels in both genotypes. However, the effect of dexmedetomidine on noradrenaline release was attenuated in the alpha(2A) -adrenoceptor knockout mice, whereas the effect on dopamine release did not differ between the genotypes. The first handling episode increased noradrenaline and dopamine levels to the same extent in both genotypes. However, in alpha(2A) -adrenoceptor knockout mice the noradrenaline and dopamine levels remained elevated in the samples following the first handling whilst, in the control mice, transmitter levels returned to baseline levels. In control mice the handling-induced peak noradrenaline and dopamine levels were lower after the administration of dexmedetomidine than during the first handling episode, but in alpha(2A) -adrenoceptor knockout mice no drug effect on handling-induced peak noradrenaline and dopamine levels was found. Our results suggest that the release of noradrenaline in the medial prefrontal cortex is mainly regulated via alpha(2A) -adrenoceptors, whilst other alpha-adrenoceptor subtypes play a significant role in the regulation of dopamine release.