Fig. 6. Schematic representation of the putative mechanism by which presynaptic Zn²⁺ modulates the effects of cocaine on dopamine and glutamate neurotransmission in the striatum in wild-type (WT) and ZnT3 knockout mice.

The image on the left shows the effect of synaptic Zn²⁺ on increasing cocaine’s efficacy by binding to the DAT on dopaminergic neurons. It also acknowledges the putative effects of Zn²⁺ on glutamate neurotransmission in the context of cocaine via its interaction with AMPA and NMDA receptors. The image on the right illustrates the effect of ZnT3 deletion, and consequently the loss of presynaptic Zn²⁺ release, in attenuating the effects of cocaine on striatal dopamine and glutamate neurotransmission.