کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5923594 1571168 2015 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The glucagon-like peptide 1 (GLP-1) receptor agonist exendin-4 reduces cocaine self-administration in mice
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی فیزیولوژی
پیش نمایش صفحه اول مقاله
The glucagon-like peptide 1 (GLP-1) receptor agonist exendin-4 reduces cocaine self-administration in mice
چکیده انگلیسی


- GLP-1 receptor stimulation reduces acute and chronic cocaine self-administration.
- Exendin-4 reduces cocaine-induced elevation of striatal DA and c-fos expression.
- GLP-1 receptor stimulation decreases DA D1 receptor agonist induced hyperactivity.

Glucagon-like peptide 1 (GLP-1) analogues are used for the treatment of type 2 diabetes. The ability of the GLP-1 system to decrease food intake in rodents has been well described and parallels results from clinical trials. GLP-1 receptors are expressed in the brain, including within the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Dopaminergic neurons in the VTA project to the NAc, and these neurons play a pivotal role in the rewarding effects of drugs of abuse.Based on the anatomical distribution of GLP-1 receptors in the brain and the well-established effects of GLP-1 on food reward, we decided to investigate the effect of the GLP-1 analogue exendin-4 on cocaine- and dopamine D1-receptor agonist-induced hyperlocomotion, on acute and chronic cocaine self-administration, on cocaine-induced striatal dopamine release in mice and on cocaine-induced c-fos activation. Here, we report that GLP-1 receptor stimulation reduces acute and chronic cocaine self-administration and attenuates cocaine-induced hyperlocomotion. In addition, we show that peripheral administration of exendin-4 reduces cocaine-induced elevation of striatal dopamine levels and striatal c-fos expression implicating central GLP-1 receptors in these responses. The present results demonstrate that the GLP-1 system modulates cocaine's effects on behavior and dopamine homeostasis, indicating that the GLP-1 receptor may be a novel target for the pharmacological treatment of drug addiction.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Physiology & Behavior - Volume 149, 1 October 2015, Pages 262-268
نویسندگان
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