Fig. (2).

(A) Major neurotransmitter pathways targeted by medications tested for efficacy in methamphetamine use disorder (MUD) and brain areas connected by these pathways. A key brain area mediating drug reward/reinforcement and drug cravings is the nucleus accumbens. This area receives dopaminergic innervations (red) from the ventral tegmental area. This area sends dopaminergic projections also to the prefrontal cortex, hippocampus and amygdala. The nucleus accumbens receives glutamatergic input (green) from the prefrontal cortex, hippocampus and amygdala. GABAergic (blue) interneurons within the ventral tegmental area regulate the activity of dopaminergic neurons projecting to the nucleus accumbens. (B) Methamphetamine (METH) action at the dopaminergic terminal. METH enters the dopaminergic terminal via the dopamine transporter (DAT) where it subsequently enters dopamine storage vesicles via vesicular monoamine transporter 2 (VMAT2) (black arrows). Dopamine is released from the storage vesicles to the cytoplasm and subsequently to the synaptic cleft via METH-induced reversal of the DAT and activates postsynaptic dopamine D1 and D2 receptors. (A higher resolution/colour version of this figure is available in the electronic copy of the article).