Comparisons of behavioral phenotypes in multiple methods of serotonin deficiency in the rat brain.

摘要

Serotonin is an important neurotransmitter in the mammalian brain. Axons from serotonergic cell bodies in the raphe nuclei project to virtually every region of the brain, influencing actions of other chemical messengers and exerting its own effects. Due to this influence, serotonin dysfunction has been implicated in the psychiatric disorders depression, schizophrenia, and autism. Myriad studies attempt to understand serotonin's role in these psychiatric disorders, although symptomatic heterogeneity autism makes this difficult. It has been shown that lower serotonin synthesis occurs in autistic patients during neonatal development. Furthermore, serotonin reuptake inhibitors ameliorate behaviors associated with autism. The results suggest that diminished brain serotonin plays a role in the behaviors of autistic patients, yet they do not explain why some reuptake inhibitors attenuate these behaviors and others do not. Could it be that there is a certain range of serotonin loss that accounts for some behaviors over others?; To explore this question, pharmacological and surgical lesions and social isolation were used to manipulate serotonin to determine if these manipulations would negatively impact exploration, motor learning, and sociability and aggravate perseveration, behaviors common in autistic patients. Since autism manifests early in life, I examined the effect age would have on the expression of these behaviors. The data showed that different manipulations produce similar behaviors although of some of the behaviors were manipulation-specific. Moreover, younger and older animals with the same type of lesion have almost completely different behavioral phenotypes, suggesting a critical window by which lesions may affect autistic-like behaviors such as sociability and perseveration. I measured binding of [3H] citalopram to serotonin transporters in areas where major raphe nuclei project: the cortex, hippocampus, and striatum, to determine the extent of serotonergic loss. The data from PCA-exposed animals showed there was distinct loss in serotonin. However, the data did not reveal any reduction in serotonin in socially isolated animals and scant reduction in the cortex of olfactory bulbectomized animals. The results of this experiment provide insight into what might be occurring in the brains of autistic patients in relation to serotonin, providing more understanding to develop better strategies to address autism.