The effect of methamphetamine on seizure threshold and epileptogenesis.

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Title The effect of methamphetamine on seizure threshold and epileptogenesis.
Publication Type dissertation
School or College School of Medicine
Department Neurology
Author Qiao, Liang
Date 2007-12
Description Epilepsy, one of the most common chronic neurological disorders, is characterized by recurrent spontaneous seizures. Seizures result from many causes including genetic or developmental defects, traumatic brain injury, substance abuse, infection, fever, metabolic disturbances, withdrawal symptoms and space-occupying lesions in the brain. Methamphetamine (METH), a schedule II drug, leads to seizures that are mostly due to overdose. In recent years, there has been a rapid increase in METH-related emergencies, in which seizures are one of the most common and fatal symptoms. It is hypothesized in this dissertation that METH affects seizure threshold and epileptogenesis through its modulation of monoamine systems. This hypothesis was tested by completing the following specific aims. Specific Aim 1 investigated the effect of METH on seizure threshold in two acute electroconvulsant (tonic hindlimb extension & 6-Hz psychomotor) and two acute chemoconvulsant (pentylenetetrazol & kainic acid) models. The results suggest that METH alters seizure threshold in a model-specific manner: METH increased the tonic hindlimb extension threshold while it decreased the threshold for 6-Hz psychomotor seizures and pentylenetetrazol-induced clonus; the threshold for kainic acid-induced seizures was not affected by METH treatment. Specific Aim 2 explored the role of dopaminergic receptor modulation in METH-induced change of electroconvulsant seizure threshold. The data demonstrated that the D-1 antagonist SCH-23390 displayed a synergistic effect with METH in modulating tonic hindlimb extension and 6-Hz psychomotor seizure threshold, whereas an antagonistic effect was observed between the D-2 antagonist eticlopride and METH. Moreover, eticlopride blocked the SCH-23390/METH synergism in a dose-dependent manner. Specific Aim 3 assessed the effect of METH on amygdala kindling acquisition and brain monoamine levels. Multiple METH treatment facilitated epileptogenesis by enhancing the amygdala kindling acquisition rate. Serotonin (5-HT) was found to be depleted in the limbic system (amygdala and hippocampus) and striatum. Dopamine (DA) concentration was reduced in the striatum. However, there was no change in norepinephrine (NE) levels. In summary, METH modulates seizure threshold and facilitates epileptogenesis, which depends on its interaction with monoaminergic neurotransmission. Results obtained from this study provide important information to our understanding of the mechanisms underlying METH-related convulsions.
Type Text
Publisher University of Utah
Subject Pharmacology; Methamphetamine; Epileptogenesis
Subject MESH Epilepsy; Seizures
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "The effect of methamphetamine on seizure threshold and epileptogenesis." Spencer S. Eccles Health Sciences Library. Print version of "The effect of methamphetamine on seizure threshold and epileptogenesis." available at J. Willard Marriott Library Special Collection. RM31.5 2007 .Q25.
Rights Management © Liang Qiao.
Format application/pdf
Format Medium application/pdf
Identifier us-etd2,9279
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
ARK ark:/87278/s6tm7rkj
Setname ir_etd
ID 192210
Reference URL https://collections.lib.utah.edu/ark:/87278/s6tm7rkj
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