Critical role for ventral tegmental glutamate in preference for a cocaine-conditioned environment

Cocaine administration induces glutamatergic activation within the mesolimbic-accumbens system. This activation has been linked to the behavioraleffects of cocaine and recently to the induction of long-term potentiation in dopamine neurons within the ventraltegmentalarea (VTA). We sought to determine if glutamate receptor activation is also crucialto the development of a conditioned placepreference (CPP) to cocaine's rewarding effects. Two groups of rats were given intra-VTA injections of either vehicle ora combination ofNMDA (N-methyl-D-aspartate) and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor antagonists (AP50.24nmolplus CNQX 0.12nmolper side) priorto each cocaine place-conditioning trial. Microinjections of the glutamate antagonistscompletely blocked the development of a cocaine CPP when given within, but not when given outside of, the VTA. These data indicatethat glutamatergic activity in the VTA may be crucialfor learning to associate environmentalstimuliwith cocaine exposure.