Interactions between dopamine and excitatory amino acids in behavioral sensitization to psychostimulants

Mesoaccumbens dopamine transmission at least partly mediates the initiation and expression of behavioral sensitization to psychostimulants. The initiation arises from an action by psychostimulants on dopamine cell bodies in the ventral tegmental area (VTA) while the expression of behavioral sensitization involves enhanced pre- and postsynaptic dopamine transmission in the nucleus accumbens. Evidence is emerging that excitatory amino acid (EAA) transmission is also involved in behavioral sensitization to psychostimulants. In this report, evidence is presented that the initiation of behavioral sensitization involves stimulation of NMDA receptors in the VTA which may occur via enhanced presynaptic release of EAAs following activation of D1 receptors. It is further posited that EAA transmission in the nucleus accumbens may promote the expression of sensitization by increasing presynaptic dopamine release and modulating the postsynaptic actions of dopamine.