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。

IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES Behavioural Pharmacology Pub Date : 2023-09-01 Epub Date: 2023-07-11 DOI:10.1097/FBP.0000000000000740
Jeffrey William Grimm, Frances Sauter, Derek MacDougall, Emily Spaulding, Kyra Stensgaard, Mason Hardy, Kyle Griffin, Rebecca Marx
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引用次数: 0

摘要

目的:mGlu2/3受体激动剂LY379268减少雄性大鼠的蔗糖寻求,但不减少蔗糖摄取。这项研究探讨了这种影响在两性之间的普遍性。此外,还评估了该药物对接受蔗糖的动机的影响。方法:成年雄性和雌性Long-Evans大鼠(N = 91)在三个实验中用LY379268进行挑战:(1)固定比率(FR)强化计划(采取)、(2)先前在FR上强化的反应的消失(寻求)或(3)在渐进比率(PR)强化计划中强化的反应(动机)。对于每个实验,大鼠首先对FR上的10%液体蔗糖进行反应,每天10次,每次2小时。对于PR研究,随后进行PR培训,每天7次,每次3小时。然后用LY379268(0、1.5、3和6 mg/kg;IP;30分钟预处理)、随后FR(实验1和2)或PR(实验3)反应的三个再获取日。结果:雌性大鼠对蔗糖对FR和PR的反应更大。LY379268在所有三个实验中都降低了反应。LY379268对蔗糖对FR的攻击产生倒U型功能,而对PR的消光反应和对蔗糖的反应呈剂量依赖性降低,PR对1.5 mg/kg剂量。该药物对蔗糖定向反应没有性别依赖性影响。结论:LY379268对雄性和雌性大鼠的蔗糖抗摄取、寻求和动机作用支持谷氨酸调节作为一种抗食欲药物治疗的进一步评估。
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The mGlu2/3 agonist LY379268 reduces sucrose taking, seeking, and motivation in male and female rats.

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.

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来源期刊
Behavioural Pharmacology
Behavioural Pharmacology 医学-行为科学
CiteScore
3.40
自引率
0.00%
发文量
84
审稿时长
6-12 weeks
期刊介绍: Behavioural Pharmacology accepts original full and short research reports in diverse areas ranging from ethopharmacology to the pharmacology of schedule-controlled operant behaviour, provided that their primary focus is behavioural. Suitable topics include drug, chemical and hormonal effects on behaviour, the neurochemical mechanisms under-lying behaviour, and behavioural methods for the study of drug action. Both animal and human studies are welcome; however, studies reporting neurochemical data should have a predominantly behavioural focus, and human studies should not consist exclusively of clinical trials or case reports. Preference is given to studies that demonstrate and develop the potential of behavioural methods, and to papers reporting findings of direct relevance to clinical problems. Papers making a significant theoretical contribution are particularly welcome and, where possible and merited, space is made available for authors to explore fully the theoretical implications of their findings. Reviews of an area of the literature or at an appropriate stage in the development of an author’s own work are welcome. Commentaries in areas of current interest are also considered for publication, as are Reviews and Commentaries in areas outside behavioural pharmacology, but of importance and interest to behavioural pharmacologists. Behavioural Pharmacology publishes frequent Special Issues on current hot topics. The editors welcome correspondence about whether a paper in preparation might be suitable for inclusion in a Special Issue.
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