GABA transporters regulate synaptic GABA levels and dysfunctions in this system might result in psychiatric disorders. The endocannabinoid system (ECS) is the main circuit breaker in the nervous system and may alter noradrenaline (NA) communication, which in turn modulates the release of GABA. However, a close relationship between these systems has not been recognized. We asked whether NA and ECS might control extracellular GABA levels in slices of frontal cortex (FC) of adolescent Swiss mice with 40 days after birth (PN40). Here we show that NA and isoproterenol (ISO), a beta-adrenergic agonist, increased [³H]-GABA uptake in mice FC, while alpha₁-adrenergic agonist phenylephrine had no effect. As GAT-1 is expressed and fully functional at the FC, addition of NO-711, a GAT-1 inhibitor, dose dependently blocked [³H]-GABA uptake. The increase of [³H]-GABA uptake induced by ISO was also blocked by NO-711. [³H]-GABA release induced by 80 mM KCl was reduced by NO-711, but not by removal of Ca²⁺. ISO also increased cyclic AMP (cAMP) levels and addition of WIN 55,212-2, a mixed CB₁/CB₂ receptor agonist, inhibited the effect of ISO in GABA uptake increase, GAT-1 expression and cAMP levels compared to control. Our data show that GABA transport increased by NA and ISO is negatively regulated by cannabinoid receptor agonist WIN55,212-2.

GABA转运蛋白调节突触GABA的水平，该系统功能障碍可能导致精神病。内源性大麻素系统（ECS）是神经系统的主要断路器，可能会改变去甲肾上腺素（NA）的通讯，进而调节GABA的释放。但是，尚未认识到这些系统之间的紧密关系。我们询问了NA和ECS是否可以控制出生后40天（PN40）的青春期瑞士小鼠额叶皮质（FC）切片中的细胞外GABA水平。在这里，我们显示NA和异丙肾上腺素（ISO），一种β-肾上腺素能激动剂，增加了小鼠FC中[ ³ H] -GABA的摄取，而alpha ₁-肾上腺素能激动剂去氧肾上腺素没有作用。由于GAT-1在FC上表达并完全发挥功能，因此添加GAT-1抑制剂NO-711可以剂量依赖性地阻断[ ³ H] -GABA的吸收。NO-711也阻止了ISO诱导的[ ³ H] -GABA吸收的增加。NO-711降低了80 mM KCl诱导的[ ³ H] -GABA的释放，但并未去除Ca ²⁺。ISO还提高了循环AMP（cAMP）的水平，并添加了WIN 55,212-2（混合的CB ₁ / CB _2）受体激动剂，与对照组相比，抑制了ISO在GABA摄取增加，GAT-1表达和cAMP水平方面的作用。我们的数据表明，NA和ISO增加的GABA转运受到大麻素受体激动剂WIN55,212-2的负调控。