D2 receptor antagonism enhances cocaine-induced behavioral sensitization in female, but not male Japanese quail ( Coturnix japonica ).

Sex differences in cocaine-induced behaviors are well established. In rodents, females show enhanced locomotion to cocaine over multiple trials compared with males, a behavioral response known as sensitization. Estradiol enhances cocaine-induced sensitization in female rats by agonizing dopaminergic activity within the brain. In female quail, cocaine does not increase locomotion regardless of increased estradiol. A higher D2:D1 dopamine receptor ratio in quail compared with rodents may explain this sex and species difference. The goal of the present work was to investigate the role of D2 receptors in cocaine-induced locomotion and sensitization in Japanese quail and to determine whether a greater D2 receptor availability contributed to the lack of cocaine-induced sensitization in female quail found in previous studies. Male and female quail were administered 0, 0.03, 0.05, or 0.07 mg/kg of eticlopride (Eti) followed by 10 mg/kg of cocaine or saline then immediately placed in open-field chambers. Distance traveled was recorded for 30 min daily for 7 days. In female quail, cocaine-induced sensitization was observed with 0.03 or 0.05 mg/kg Eti, but not in cocaine-only females. In male quail, cocaine-induced sensitization was observed similar to previous research. However, Eti did not enhance cocaine-induced locomotion or produce sensitization in male quail. The D2 receptor likely mediates cocaine's motor stimulating effects in quail. In females, this effect is more pronounced. Since high D2 availability is protective against stimulant abuse, Japanese quail may be a useful model for investigating the role of the D2 receptor in cocaine addiction, but further research is needed.