In addition to the strong association evident between GluA1 and PSD-95, the relationship detected between Homer and dynamin-3 in heroin abusers would also strongly suggest enhanced availability of AMPA receptors at glutamatergic synapses and thus potentiated synaptic transmission. Homer is concentrated to the PSD and together with dynamin-3 is localized to the lateral spine membrane with a distribution that spans the PSD and endocytic zone (32, 45). In vitro studies have demonstrated that the physical link between dynamin-3 and Homer positions the endocytic zone near the PSD to maintain cycling AMPA receptors at the synapse (31, 32). Those investigations provide clear evidence that synapses lacking a PSD directly linked to the endocytic zone results in depletion of AMPA receptors at the synapse thereby leading to a reduction of excitatory synaptic transmission. Our data demonstrating that the physical coupling between Homer 1b/c and dynamin-3 was positively correlated to blood morphine levels would be in line with an upregulation of AMPA transmission upon drug intake.
