Sex differences in sucrose-induced locomotor sensitization and cross-sensitization with the D2/D3 agonist quinpirole in rats

Background : Female-biased sex differences are known to exist in the prevalence of eating-related disorders and the experience of food cravings. Similarly, in rodents, females display a greater preference and motivation for the highly palatable sweet food, sucrose, than do males. Locomotor sensitization, the increase in locomotor activity that occurs with repeated administrations of drugs of abuse, is thought to occur through drug-induced sensitization of the mesolimbic dopamine pathway and reflect enhancements in drug craving. Pre-exposure to sucrose has been shown to enhance locomotor sensitization induced by dopaminergic agonists, however, it is unknown if sex differences exist in this effect. Methods : Female (n = 16) and male (n = 16) Long-Evans rats received 30 min daily access to sucrose (0.3 M) or water for nine consecutive days followed by daily administration of the D2/D3 agonist, quinpirole (0.5 mg/kg), for nine consecutive days. On the first, fifth, and ninth day of the sucrose and quinpirole phases, rats were placed in automated activity monitors for 30 min after fluid access and drug administration, respectively, to assess locomotor activity. Mixed model analyses of variance were used to evaluate differences in locomotor activity between Female + Sucrose, Female + Water, Male + Sucrose, and Male + Water treated rats. Results : Female + Sucrose rats showed significantly greater weight-adjusted fluid consumption of sucrose than did Male + Sucrose rats. Female + Sucrose rats exhibited a significant increase in locomotor activity across the sucrose phase and significantly greater locomotor activity relative to other groups. In the quinpirole phase, both groups pre-exposed to sucrose (Female + Sucrose, Male + Sucrose) showed greater activity than their same-sex control pre-exposed to water (Female + Water, Male + Water). Further, both female groups generally displayed greater activity than both male groups in the quinpirole phase. Conclusions : A female-biased sex difference was identified in the effect of locomotor sensitization induced by sucrose (0.3 M), but not for sucrose pre-exposure on quinpirole sensitization (0.5 mg/kg). These results suggest that differences may exist between sexes in the mesolimbic response to sucrose, perhaps underlying sex differences in food cravings and eating-related disorder prevalence.