The D-2 receptor is critical in mediating opiate motivation only in opiate-dependent and withdrawn mice

According to the dual systems model for opiate reward, dopamine mediates op iate motivation when an animal is in a deprived motivational state (i.e. op iate-dependent and in withdrawal) and not when an animal is in a nondeprive d state (i.e. previously drug-naive). To determine the role of the D-2 dopa mine receptor subtype in mediating opiate motivation, we examined the behav iour of N5 congenic D-2 receptor knockout mice and their wild-type siblings in opiate-naive and opiate-dependent and withdrawn place conditioning para digms. Opiate-naive D-2 receptor knockout mice demonstrated acquisition of morphine-conditioned place preference but failed to acquire place preferenc e when conditioned in the deprived state. We propose that D-2 receptor func tion is critical in mediating the motivational effects of opiates only when the animal is in an opiate-dependent and withdrawn motivational state. The se findings also underscore the important influence of the genetic backgrou nd to a given phenotype, as evidenced by the observation that increasing th e allelic contribution from the 129/SvJ strain abolishes morphine place pre ference in C57BL/6 wild-type mice.