Figure 2.

The AMPA glutamate receptor subunit, GluR2, is a putative target for ΔFosB. Shown is how ΔFosB-mediated induction of GluR2 may alter the physiological responsiveness of nucleus accumbens neurons and lead to sensitized responses to drugs of abuse. According to this scheme, drugs of abuse produce their acute reinforcing effects via inhibition of nucleus accumbens neurons. With repeated exposure, the drugs induce ΔFosB, which regulates numerous target genes, including GluR2. This increases the proportion of AMPA receptors (AMPA-R) on nucleus accumbens neurons that contain the GluR2 subunit, which causes reduced overall AMPA current and reduced Ca²⁺ current. This reduced excitability could render the neurons more sensitive to the acute inhibitory effects of the drugs and thereby to the drugs' reinforcing effects.