title: The alteration of 5-HT(2A) and 5-HT(2C) receptors is involved in neuronal apoptosis of goldfish cerebellum following traumatic experience.
abstract: 5-HT receptor changes remain controversial in posttraumatic stress disorder (PTSD) models. This study looks at the relationship between traumatic injuries and the alterations in 5-HT(2A) and 5-HT(2C) receptors in the goldfish brain. The effect of treatment with doxepin and fluoxetine, known to be selective serotonin reuptake inhibitor (SSRI) antidepressants, on 5-HT receptor expression in goldfish with fin ablation was also investigated. We demonstrated that fin ablation induced anxiety-like behavioural alterations and significant up-regulation of c-fos expression in goldfish cerebellum. The behavioural alterations correlated well with an increased expression of 5-HT(2A) receptors in the cerebellum of the fish with traumatic injury. An increase in the number of apoptotic cells and a higher caspase-8 protein level was present in the brains of goldfish with fin ablation compared to the control. Our findings suggest that neuronal apoptosis occured in the cerebellum as a result of fin ablation and may be related to the alterations of 5-HT(2A) and 5-HT(2C) levels and that the beneficial clinical effects of doxepin/fluoxetine treatment are due to the down-regulation of 5-HT(2A) and up-regulation of 5-HT(2C) receptors in the brain.
authors.affiliation: Division of Plastic and Reconstructive Surgery, The Second Affiliated Hospital, Medical College, Zhejiang University, Hangzhou, China. huxueqing@zju.edu.cn
authors.forename: Xueqing
authors.initials: X
authors.lastname: Hu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Hu
authors.forename: John A
authors.initials: JA
authors.lastname: Rudd
authors.forename: Shucai
authors.initials: S
authors.lastname: Ling
authors.forename: Fangzhen
authors.initials: F
authors.lastname: Jiang
authors.forename: Henry
authors.initials: H
authors.lastname: Davies
authors.forename: Marong
authors.initials: M
authors.lastname: Fang
mesh_terms: D000704:Analysis of Variance; D058500:Animal Fins / Q000502:physiology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D015153:Blotting, Western; D001930:Brain Injuries / Q000473:pathology* / Q000523:psychology*; D002531:Cerebellum / Q000293:injuries* / Q000473:pathology; D004316:Doxepin / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D006054:Goldfish / Q000502:physiology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000502:physiology*; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013313:Stress Disorders, Post-Traumatic / Q000473:pathology / Q000523:psychology; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: D000929:Antidepressive Agents, Tricyclic; D004316:Doxepin; D005473:Fluoxetine; D016760:Proto-Oncogene Proteins c-fos; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D017367:Selective Serotonin Reuptake Inhibitors; D051025:bcl-Associated Death Protein