Conditioned place preference (CPP) is a conditioning procedure whereby an animal is injected with a drug in one environmental context and with vehicle in another context (the conditioning phase). After conditioning, the animal is then tested for CPP expression by allowing it to choose between drug- and vehicle-paired contexts. If the animal spends more time in the drug-paired context, the drug is thought to be rewarding. Activation of ERK is necessary for the development of drug-induced CPP. Pretreatment with systemic injections of SL327 during the conditioning phase prevents the development of cocaine-,16 methamphetamine-,35 THC-,32 and morphine-induced CPP.44 A different MEK inhibitor, PD98059, infused directly into the NAc, also inhibits the development of methamphetamine-induced CPP.22 Established cocaine CPP increases phosphorylation of ERK, CREB, and Elk-1 in the rat NAc. These changes are attenuated by intra-VTA injections of U0126.52 Thus ERK activity appears to be involved in mediating the rewarding properties of psychostimulants, cannabinoids, and opiates.
