mGlu2/3 激动剂 LY379268 减少雄性和雌性大鼠的蔗糖摄取、寻求和动机。
The mGlu2/3 agonist LY379268 reduces sucrose taking, seeking, and motivation in male and female rats.
机构信息
Department of Psychology and Program in Behavioral Neuroscience, Western Washington University, Bellingham, Washington, USA.
出版信息
Behav Pharmacol. 2023 Sep 1;34(6):340-349. doi: 10.1097/FBP.0000000000000740. Epub 2023 Jul 11.
OBJECTIVES
The mGlu2/3 receptor agonist LY379268 reduces sucrose-seeking, but not sucrose-taking, in male rats. This study explored the generality of this effect across the sexes. In addition, the effect of the drug on motivation to receive sucrose was assessed.
METHODS
Adult male and female Long-Evans rats ( N = 91) were challenged with LY379268 in three experiments: (1) a fixed ratio (FR) schedule of reinforcement (taking), (2) extinction of responding previously reinforced on the FR (seeking) or (3) responding reinforced on a progressive ratio (PR) schedule of reinforcement (motivation). For each experiment, rats first responded to 10% liquid sucrose on an FR in 10 daily 2-h sessions. For the PR study, this was followed by training on a PR for 7 daily 3-h sessions. Rats were then challenged in a counterbalanced order with LY379268 (0, 1.5, 3 and 6 mg/kg; IP; 30-min pretreatment) on test days, followed by either three reacquisition days of FR (experiments 1 and 2) or PR (experiment 3) responding.
RESULTS
Female rats responded more to sucrose on the FR and PR. LY379268 reduced responding in all three experiments. LY379268 challenge to sucrose taking on the FR produced an inverted U-shaped function while extinction responding and responding for sucrose on the PR were decreased dose-dependently, with PR responding insensitive to the 1.5 mg/kg dose. There were no sex-dependent effects of the drug on sucrose-directed responding.
CONCLUSIONS
The sucrose anti-taking, -seeking, and -motivation effects of LY379268 across male and female rats support further evaluation of glutamate modulation as an antiaddiction pharmacotherapy.
目的
mGlu2/3 受体激动剂 LY379268 可减少雄性大鼠对蔗糖的觅药行为，但不减少其摄食行为。本研究旨在探究该效应在不同性别间的普遍性。此外，还评估了药物对获得蔗糖动机的影响。
方法
成年雄性和雌性 Long-Evans 大鼠（N=91）在三项实验中接受 LY379268 处理：（1）固定比率（FR）强化程序（摄食），（2）之前在 FR 上强化的反应消退（觅药），或（3）在渐进比率（PR）强化程序下的反应（动机）。对于每项实验，大鼠首先在 10 个 2 小时的每日测试中对 10%的液体蔗糖进行 FR 反应。对于 PR 研究，在接下来的 7 个 3 小时的每日测试中进行 PR 训练。然后，大鼠以平衡的顺序接受 LY379268（0、1.5、3 和 6mg/kg；腹腔注射；30 分钟预处理）的挑战，随后进行 FR（实验 1 和 2）或 PR（实验 3）反应的 3 天重新获得测试。
结果
雌性大鼠在 FR 和 PR 上对蔗糖的反应更多。LY379268 在所有三项实验中均减少了反应。LY379268 对 FR 上蔗糖摄食的挑战产生了一个倒 U 形函数，而消退反应和 PR 上蔗糖的反应则呈剂量依赖性减少，PR 反应对 1.5mg/kg 剂量不敏感。药物对蔗糖导向反应没有性别依赖性影响。
结论
LY379268 在雄性和雌性大鼠中对蔗糖的抗觅药、抗觅药和抗动机作用支持进一步评估谷氨酸调节作为一种抗成瘾药物治疗。
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