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    MODIFICATION OF PINEALECTOMY-INDUCED SEIZURES IN RESPONSE TO NEUROPHARMACOLOGICAL ALTERATIONS OF CATECHOLAMINE FUNCTION IN THE RAT.

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    Author
    STOCKMEIER, CRAIG ALLEN.
    Issue Date
    1983
    Keywords
    Catecholamines -- Physiological effect.
    Epilepsy -- Etiology -- Animal models.
    Neurotransmitters -- Physiological effect.
    Noradrenaline -- Physiological effect.
    
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    Publisher
    The University of Arizona.
    Rights
    Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
    Abstract
    Removal of the pineal gland from partially parathyroidectomized rats produces stereotyped violent seizures. Inasmuch as the neurotransmitter norepinephrine (NE) has been implicated in this experimental paradigm, the purpose of this study was to investigate the effect of specific alterations in catecholamine function on convulsions produced by pinealectomy (PinX). Additionally, the role of various pineal substances, sex differences and the caging paradigm in the convulsive response was studied. Male and female rats (grouped five per cage) were found to respond similarly to the convulsive stimulus of parathyroidectomy followed by PinX. Neither implants of melatonin nor ventricular injections of arginine vasotocin in isolated and grouped rats, respectively, produced consistent changes in convulsions from PinX. The method of caging the rats after PinX, however, dramatically influenced seizures. Isolated rats (one per cage) convulsed significantly later after PinX and did so less often than grouped (five per cage) controls. NE neurotransmission appears to play a strong role in influencing PinX-induced seizures. Augmenting NE function with desipramine suppressed seizures. Convulsions were enhanced by the (beta)-receptor antagonist timolol, while neonatal injections of the catecholamine neurotoxin 6-OHDA potentiated seizures so markedly that many rats died from just one convulsion. NE levels were significantly reduced in the telencephalons and increased in the brain stems of sham-pinealectomized rats which had also received neonatal 6-OHDA; telencephalic levels of DA were elevated by 6-OHDA. Both the proconvulsant effects of 6-OHDA and the alterations it produced in central catecholamine levels were prevented, for the most part, by pretreatment with DMI. Altering both NE and DA function with L-dihydroxyphenylalanine, (alpha)-methyl-p-tyrosine, FLA-63 or reserpine did not significantly affect PinX-induced seizures in isolated rats. NE appears to play a strong role in modulating PinX-induced seizures; however, a deficit in NE function per se does not seem to be the fundamental cause of the seizures since sham-pinealectomized rats having lowered NE and/or DA function did not convulse.
    Type
    text
    Dissertation-Reproduction (electronic)
    Degree Name
    Ph.D.
    Degree Level
    doctoral
    Degree Program
    Anatomy
    Graduate College
    Degree Grantor
    University of Arizona
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    Dissertations

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