The D2 receptor is critical in mediating opiate motivation only in opiate-dependent and withdrawn mice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 opiate motivation when an animal is in a deprived motivational state (i.e. opiate-dependent and in withdrawal) and not when an animal is in a nondeprived state (i.e. previously drug-naive). To determine the role of the D-2 dopamine receptor subtype in mediating opiate motivation, we examined the behaviour of N5 congenic D-2 receptor knockout mice and their wild-type siblings in opiate-naive and opiate-dependent and withdrawn place conditioning paradigms. Opiate-naive D-2 receptor knockout mice demonstrated acquisition of morphine-conditioned place preference but failed to acquire place preference when conditioned in the deprived state. We propose that D-2 receptor function is critical in mediating the motivational effects of opiates only when the animal is in an opiate-dependent and withdrawn motivational state. These findings also underscore the important influence of the genetic background to a given phenotype, as evidenced by the observation that increasing the allelic contribution from the 129/SvJ strain abolishes morphine place preference in C57BL/6 wild-type mice.