Department of Psychology and Program in Behavioral Neuroscience, Western Washington University, 516 High Street, Bellingham, WA, 98225-9172, USA.
Biol Sex Differ. 2022 Jan 11;13(1):3. doi: 10.1186/s13293-022-00412-8.
There are sex differences in addiction behaviors. To develop a pre-clinical animal model to investigate this, the present study examined sex differences in sucrose taking and seeking using Long-Evans rats.
Five experiments were conducted using separate groups of subjects. The first two examined sucrose or saccharin preference in two-bottle home cage choice tests. Experiment three assessed sucrose intake in a binge model with sucrose available in home cage bottles. Experiments four and five utilized operant-based procedures. In experiment four rats responded for sucrose on fixed and progressive ratio (FR, PR) schedules of reinforcement over a range of concentrations of sucrose. A final component of experiment four was measuring seeking in the absence of sucrose challenged with the dopamine D1 receptor antagonist SCH23390. Experiment five assessed responding for water on FR and PR schedules of reinforcement.
When accounting for body weight, female rats consumed more sucrose than water; but there was no sex difference in saccharin preference over a range of saccharin concentrations. When accounting for body weight, females consumed more sucrose than males in the binge model, and only females increased binge intake over 14 days of the study. Females responded at higher rates for sucrose under both FR and PR schedules of reinforcement. Females responded at higher rates in extinction (seeking); SCH23390 reduced sucrose seeking of both females and males. Females responded at higher rates for water on FR and PR schedules than males, although rates of responding were low and decreased over sessions.
Across bottle-choice, binge intake, and operant procedures, female Long-Evans rats consumed more sucrose and responded at higher rates for sucrose. Although females also responded more for water, the vigor of responding did not explain the consistent sex difference in sucrose taking and seeking. The sex difference in sucrose taking was also not explained by sweet preference, as there was no sex difference in saccharin preference. These data provide a pre-clinical model to further evaluate sex differences in addiction behaviors and manipulations designed to reduce them.
成瘾行为存在性别差异。为了开发一种用于研究该问题的临床前动物模型，本研究使用长爪沙鼠考察了蔗糖摄入和寻求的性别差异。
本研究使用独立的实验组进行了五项实验。前两项实验在双瓶笼式选择测试中检查了蔗糖或糖精偏好。实验三评估了在笼内瓶中提供蔗糖的 binge 模型中的蔗糖摄入量。实验四和实验五采用操作性程序。在实验四中，大鼠根据蔗糖浓度的变化，在固定和递增比例（FR，PR）强化程序上对蔗糖进行反应。实验四的最后一部分是在没有蔗糖的情况下测量多巴胺 D1 受体拮抗剂 SCH23390 引发的寻求行为。实验五评估了大鼠在 FR 和 PR 强化程序上对水的反应。
在考虑体重的情况下，雌性大鼠比雄性大鼠消耗更多的蔗糖；但在一系列蔗糖浓度下，雌性大鼠对糖精的偏好没有性别差异。在考虑体重的情况下，雌性大鼠在 binge 模型中消耗的蔗糖多于雄性大鼠，并且只有雌性大鼠在研究的 14 天内增加了 binge 摄入量。雌性大鼠在 FR 和 PR 强化程序下对蔗糖的反应率更高。雌性大鼠在 SCH23390 引发的蔗糖寻求中表现出更高的反应率，而雄性大鼠也表现出了降低的蔗糖寻求反应率。在 FR 和 PR 强化程序下，雌性大鼠对水的反应率高于雄性大鼠，尽管反应率较低，并且随着实验的进行而降低。
在瓶选、 binge 摄入和操作性程序中，雌性长爪沙鼠消耗了更多的蔗糖，并且对蔗糖的反应率更高。尽管雌性大鼠对水的反应也更多，但蔗糖摄入和寻求的性别差异并不能用反应力度来解释。蔗糖摄入的性别差异也不能用甜偏好来解释，因为雌性大鼠和雄性大鼠在糖精偏好上没有差异。这些数据提供了一种临床前模型，可进一步评估成瘾行为中的性别差异，并评估旨在减少这些差异的干预措施。
