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The effect of repeated early injury on reward-related processing in the adult rat.

By L.A. Low

Abstract

Pain during early life can affect the developing central nervous system, leading to altered neural function in the adult organism. In this thesis, I investigate the long-term effects of repeated early pain on reward-related processing in the adult rat. I hypothesised that the reward system was likely to be sensitive to early activation of pain pathways, as the brain systems involved in both pain and reward overlap extensively, and virtually all centrally acting analgesic drugs are also drugs of reward. To begin, I investigate the extent to which the developing reward system is activated by a classic analgesic and drug of abuse, morphine. Comparing neonatal and adult activation of the dopaminergic system, results show that a single morphine challenge activates neonatal reward pathways, but that there are qualitative differences in the neonatal response to repeated morphine. Next, I show how reward-related behaviours of adult animals repeatedly injured as neonates differ from those of uninjured littermates, and finally propose the lateral hypothalamic orexin system as a biomarker reflecting this behaviour. The results provide evidence that neonatal injury interferes with the normal development of reward systems during a critical period of development, resulting in characteristic changes in reward behaviour and cell signalling in the adult animal.

OAI identifier: oai:RePEc:ner:ucllon:http://discovery.ucl.ac.uk/20236/
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