“…Local effects of drugs of abuse on VTA neurons appear to be necessary and sufficient to trigger sensitization, because repeated local microinjections of amphetamine or morphine into the VTA elicit behavioral sensitization (Kalivas and Duffy, 1987;Kalivas and Weber, 1988;Druhan et al, 1993;Vezina, 1993;Cador et al, 1995) and microinjections of specific DA or glutamate receptor antagonists into the VTA prevent sensitization (Vezina and Stewart, 1989;Kalivas and Alesdatter, 1993;Bjijou et al, 1996;Kim and Vezina, 1998;Cador et al, 1999;Vezina and Queen, 2000). Several lines of evidence support the idea that synaptic plasticity at glutamate synapses in the VTA plays a key role in triggering sensitization and other neuroadaptations that may contribute to the development of addiction (Schenk and Snow, 1994;White, 1996;Carlezon et al, 1997;Ungless et al, 2001;Hyman and Malenka, 2001;Kauer, 2004). Most recently it has been demonstrated that the glutamate receptor complement (AMPAR/NMDAR ratio) at excitatory synapses onto VTA DA neurons is altered 24 h after exposure to several distinct drugs of abuse, but not by centrally acting drugs that are not addictive (Ungless et al, 2001;Saal et al, 2003).…”