To assess the dependence liability of morphine and subsequent effects of ondansetron on such dependence, a counter-balanced conditioned place preference (CPP) paradigm was used [22,23]. The CPP experiments were carried out using Place Preference System (MED Associates Inc., St. Albans, Vermont, USA), which consists of three compartments; two outer compartments for active association and a middle neutral compartment. One association compartment is constructed of white opaque plastic walls with a floor made of metal rods, whereas the other compartment is made of black opaque plastic walls with a metal mesh floor. The smaller middle neutral compartment is made of gray opaque plastic walls and floor. Experiments were conducted in a dimly lit room with homogenous lighting (approximately 20 lux). The place preference apparatus is equipped with motion photosensors with data recorded through a computer running MED PC software (MED Associates Inc.). C57BL/6J mice (8−12 weeks old) were used in all experiments, which were carried out during the second half of the light phase between 13 : 00 and 18 : 00 h. On Day 0, the mice were acclimated to