期刊
NEUROPHARMACOLOGY
卷 183, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2019.107838
关键词
Psychedelics; Compulsivity; 5-HT2A receptor; 5-Hydroxytryptamine; Marble burying; Spontaneous alternation behavior
资金
- Lundbeckfonden [R263-2017-3000]
The study shows that agonism of 5-HT2AR reduces repetitive behavioral patterns, supporting the theory that this is a potential new treatment approach to disorders of cognitive or behavioral inflexibility.
5-Hydroxytryptamine 2A receptor (5-HT2AR) agonist psychedelics are increasingly recognized as potentially useful treatments of psychiatric disorders, such as obsessive-compulsive disorder, depression, anxiety, and drug dependence. There is limited understanding of the way they exert their therapeutic action, but inhibition of rigid behavior and cognition has been suggested as a key factor. To examine the role of 5-HT(2A)Rs in modulating repetitive behavior, we tested two 5-HT2AR agonists, DOI, and the selective 25CN-NBOH, in two mouse tests of compulsive-like behavior. Using adult C57BL/6JOlaHsd male mice, we examined the effects of the two compounds on digging behavior in the marble burying test and on 8-OH-DPAT-disrupted spontaneous alternation behavior in the Y-maze. Both compounds dose-dependently decreased digging behavior in the marble burying test, indicating anti-compulsivity effects, which were not related to non-specific locomotor inhibition. Both 5-HT2AR agonists also reversed 8-OH-DPAT-reduced alternation ratio in the spontaneous alternation behavior test, although the effects were less pronounced than in the marble burying test. This suggests that the 5-HT2AR promotes exploratory behavior, but that the deficit produced by 8-OH-DPAT is too excessive to be fully reversed by 5-HT2AR agonists. This study shows that agonism of 5-HT2AR reduces repetitive behavioral patterns, supporting the theory that this is a potential new treatment approach to disorders of cognitive or behavioral inflexibility. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.
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