Fig. 3.

Coordinated presynaptic and postsynaptic gene expression changes in the LH after cocaine intake escalation. The levels of the mRNAs for several synaptic proteins were altered in the LH of cocaine-escalating rats. ESC genes are indicated in bold within yellow boxes. The diagram shows their presynaptic and postsynaptic distributions and some of their possible interactions. In some cases, e.g., Map1a and PKCγ, the proteins could be present presynaptically and postsynaptically. Changes in elements of the release machinery were usually increases and could reflect changes in protein content or the result of increased synaptic contacts. SNAP-25, synaptosome-associated protein-25; ERK, extracellular signal-regulated kinase; ANIA-6, activity and neurotransmitter-induced early gene 6; VAMP, vesicle-associated membrane protein; Nf1, neurofibromin; PSD-95, postsynaptic density-95; CamKII, Ca²⁺/calmodulin protein kinase II; mGlur, metabotropic GluR; NMDAR, NMDA receptor. The differential regulation of several genes related to structural plasticity in the LH of animals with escalated cocaine intake but not in rats with stable cocaine intake suggests that a remodeling of LH circuitry involving synaptogenesis and neuritogenesis contributes to the transition to cocaine addiction.