Cue configuration effects in acquisition and extinction of a cocaine-induced place preference

A pervasive finding in animal models of substance abuse is that associations form quickly between contexts and drugs of abuse, such as cocaine. Studies of conditioned place preference (CPP) demonstrate that animals approach cues previously paired with cocaine. This is a commonly used preparation, but the configuration of the CPP apparatus differs across laboratories. Two common apparatus configurations for CPP are one compartment (in which the animal has access to the entire apparatus and spatial cues are irrelevant) or two compartments (in which access is restricted to one half of the apparatus and spatial cues are relevant). We compared the effects of acquisition and extinction of cocaine-induced CPP as a function of configuration. During CPP acquisition, C57BL/6J mice received cocaine paired with one tactile floor (conditioned stimulus; CS+) and saline paired with the other (CS-). CS+ and CS- trials occurred on alternate days in one of three configurations: one-compartment (exposure to the entire apparatus during CS+ or CS-), two-compartment consistent position (exposure to CS+ or CS- in adjacent, spatially distinct compartments), or two-compartment alternating position (exposure to CS+ or CS- in adjacent compartments that alternated spatial locations across days). A stronger preference for the CS+ floor occurred in two- versus one-compartment groups, with the strongest preference observed when cocaine was paired with alternating chamber positions. In contrast, greater loss of preference occurred after extinction in a one-compartment procedure, regardless of one- or two-compartment acquisition history. These findings suggest that a two-compartment configuration facilitated acquisition but attenuated extinction of a cocaine-induced CPP. The use of different CPP configurations may distinguish the underlying substrates and relevant cues for acquisition and extinction processes in cocaine abuse.