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p-Chlorophenylalanine-produced effects on behavior in intact and brain-damaged rats

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Document pages: 7 pages

Abstract: Introduction: Our aim was to determine if a reduction of serotonin (5-HT) synthesis in the brain would provide any protection from the behavioral alterations induced by hippocampal brain-damage. The development of open-field activity (5 minute sessions) over two weeks and the acquisition of a passive avoidance task were chosen for study.Methods:There were 3 groups of lesioned rats - those hippocampal aspiration lesions, those with only damage to the neocortex overlying the hippocampus, and a sham-operated group. Half of each group was treated 300 mg kg p-chlorphenylalanine (PCPA) for 3 successive days to deplete levels of 5-HT and the other half were given the saline vehicle alone.[Hippocampal damage is associated with increased activity in the open field and impaired learning of the step-through passive avoidance response.]Results: 1 Animals with hippocampal damage became hyperactive in the second week after operation.2 PCPA treatment had no effect on locomotion, (nor on the frequently observed thigmotaxic nature of the behavior) 3 Rearing was initially depressed after the operation, and PCPA treatment facilitated its recovery - but PCPA decreased rearing in intact animals during the second week of testing.4 Reduced levels of grooming were seen in hippocampal animals, while PCPA reduced grooming in those with neocortical damage5 The animals with hippocampal damage were impaired in witholding response in the passive avoidance task - those treated with PCPA performed even worse in not witholding the shock-reinforced step-through response. This contrasted with the intact animals, where PCPA treatment reduced the amount of footshock the animals were exposed to in the taskConclusions:.The results are consistent with a role for mesolimbic 5-HT innervation of the dorsal hippocampus having an influence on novelty-elicited responses (e.g. grooming in home vs. novel cage and investigative rearing behavior) and in modulation of the sensitivity of response to electric footshock (hypersensitive in PCPA-intact animals, hyposensitive in PCPA-hippocampal animals).

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