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Animal Models of Dementia: Their Relevance to Neurobehavioral Toxicology Testing
Pages 124-136

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From page 124...
... Although some skepticism has been expressed about the possibility of constructing such models, a generally optimistic view has prevailed (Heise, 1984; Overstreet and Russell, 1984~. For example, several investigators have used neurotoxins such as ibotenic acid, an excitotoxic amino acid, or AF64A, a putatively specific cholinergic neurotoxin, as tools for creating morphological lesions in the central nervous system (CNS)
From page 125...
... , and by individual investigators (e.g., Weiss and Laties, 1975~. These specifications include systematic manipulation of independent variables, while eliminating effects of other potentially confounding factors; precise measurement of dependent variables by
From page 126...
... This finding correlates with the observation of memory disturbances in humans exposed to organophosphate pesticides (Russell and Overstreet, 1987~. A final group of environmental challenges that might be considered for studying neurobehavioral toxicology are paradigms involving stress.
From page 127...
... These rats, which received daily low doses of DFP, had reductions in brain acetylcholinesterase activity comparable to other rats treated with higher dosages and showed comparable increased sensitivity to the muscarinic antagonist scopolamine (Chippendale et al., 1972~. ~ In a subsequent study using a daily, low-dose paradigm of DFP treatment and a challenge design, it was found that rats developed subsensitivity to muscarinic agonists within five days of starting treatment.
From page 128...
... If AF64A destroys cholinergic axons in the hippocampus, one would expect a supersensitivity to develop as an adaptation to the lost cholinergic input. We approached this question by challenging the rats with scopolamine, a muscarinic antagonist, and oxotremorine, a muscarinic agonist, and measuring locomotor activity by direct observation of line crossing in a open field chamber.
From page 129...
... Therefore, information about adaptive changes in animals exposed to neurobehavioral toxicants and the mechanisms underlying these adaptive changes can also be gathered by using similar designs. Zenick (1983)
From page 130...
... In conclusion, although active avoidance tasks can be used to measure learning in animals, many other tests must be conducted before other confounding variables can be ruled out.
From page 131...
... The continuous reinforcement schedule or various fixed ratio schedules (e.g., FR5 five presses per reward) can be very useful in testing the acute effects of various agents, but they are not particularly useful in studying learning and memory measures per se.
From page 132...
... Typically, all eight arms of the radial arm maze are baited and a trial continues until the rat consumes seven of the eight rewards. During the trial the rat may return to an alley it has already visited, thus making an error (working memory)
From page 133...
... In conclusion, both the T maze and the radial arm maze have been extremely useful in detecting disturbances of higher brain function produced by various treatments. Their main limitations are that food or water deprivation is often necessary and that they are time-consum~ng, requiring daily running in the mazes for up to several weeks.
From page 134...
... It has been suggested that studies involving such animal models can generate information of importance in supplementing knowledge in behavioral toxicology based upon clinical and epidemiological research. Animal models provide means of varying exposures to toxic substances and of controlling potentially confounding variables to extents not usually available in research involving human subjects.
From page 135...
... 1983. Ganglioside treatment improves recovery of alternation behavior after unilateral entorhinal cortex lesion.
From page 136...
... 1977. Recovery of spontaneous alternation following lesions of the entorhinal cortex in adult rats: Possible correlation to axon sprouting.


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