Nazarian Arbi, Russo Scott J, Festa Eugene D, Kraish Mohammed, Quinones-Jenab Vanya
Department of Psychology, Hunter College, City University of New York, 695 Park Avenue, New York, NY 10021, USA.
Brain Res Bull. 2004 May 30;63(4):295-9. doi: 10.1016/j.brainresbull.2004.03.004.
The rewarding effects of cocaine have been shown to be sexually dimorphic; female rats develop cocaine conditioned place preference at lower doses and with fewer cocaine pairings than male rats. The present study was conducted to determine whether D1 and D2 receptors contribute to sex differences in cocaine conditioned place preference using a 4-day paradigm. Fifteen minutes prior to receiving saline or cocaine (5mg/kg for females and 20mg/kg for males), rats were pretreated with either SCH 23390, a D1 receptor antagonist, (0.10, 0.25, or 0.50mg/kg), eticlopride, a D2 receptor antagonist, (0.05, 0.10, or 0.25mg/kg), or vehicle (saline). Antagonism of D1 receptors by SCH 23390 fully blocked cocaine conditioned place preference in male rats, while only the two lower doses of SCH 23390 blocked cocaine conditioned place preference in female rats. Conversely, antagonism of D2 receptors using eticlopride had no effect on cocaine conditioned place preference in male or female rats. Due to the known role of D1 receptors in cocaine conditioned place preference, sex differences in D1 receptor sensitivity may explain the differences observed in cocaine reward between male and female rats.
可卡因的奖赏效应已被证明具有性别差异;与雄性大鼠相比,雌性大鼠在较低剂量且可卡因配对次数较少的情况下就会形成可卡因条件性位置偏爱。本研究旨在使用一种为期4天的范式来确定D1和D2受体是否导致可卡因条件性位置偏爱的性别差异。在给予生理盐水或可卡因(雌性为5mg/kg,雄性为20mg/kg)前15分钟,大鼠分别用D1受体拮抗剂SCH 23390(0.10、0.25或0.50mg/kg)、D2受体拮抗剂艾替洛尔(0.05、0.10或0.25mg/kg)或溶剂(生理盐水)进行预处理。SCH 23390对D1受体的拮抗作用完全阻断了雄性大鼠的可卡因条件性位置偏爱,而只有两个较低剂量的SCH 23390阻断了雌性大鼠的可卡因条件性位置偏爱。相反,使用艾替洛尔拮抗D2受体对雄性或雌性大鼠的可卡因条件性位置偏爱均无影响。由于D1受体在可卡因条件性位置偏爱中已知的作用,D1受体敏感性的性别差异可能解释了雄性和雌性大鼠在可卡因奖赏方面观察到的差异。