The alteration of 5-HT2A and 5-HT2C 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.