Ashley Horner, Ph.D.
Assistant Professor of Pharmacology
Previous Institution: University of Utah College of Pharmacy
Office phone: (478) 301-4050
Mercer University School of Medicine
1550 College Street, Macon, GA 31207
There are three projects currently underway in my laboratory. The first project centers on the hypothesis that enhanced signaling in the patch compartment of the striatum, relative to the surrounding matrix compartment, underlies the development of methamphetamine-induced repetitive behaviors, and that the mu opioid receptor system contributes to the expression of these behaviors by facilitating signaling within the neurons of the patch compartment of the striatum. In support of my hypothesis, recent data from my laboratory indicates that during methamphetamine treatment, mu opioid receptors on the neurons of the patch compartment are activated resulting in increased gene expression within those neurons, and that this increased gene expression within the patch compartment is related to the development of methamphetamine-induced repetitive behaviors. My research will focus on the mechanisms by which enhanced activity of the patch compartment striatum contributes to methamphetamine-induced repetitive behaviors.
The second project in my laboratory posits that during d-amphetamine withdrawal, there is increased activity of the dynorphin system, which contributes to dysfunction of the serotonin system, and results in the inability to appropriately adapt to a stressful environment. Recent work from my laboratory shows that in certain regions of the limbic system, dynorphin expression is increased, while expression of serotonin transporters and receptors are decreased.In addition, preliminary data from my laboratory indicates that animals undergoing d-amphetamine withdrawal perform more poorly on the forced swim stress test than control animals. The alterations in the dynorphin and serotonin systems that occur following psychostimulant withdrawal, and how changes in these neurochemical systems affect one another and the ability to cope with stress is an additional focus of the research in my laboratory.
The third project currently underway in my laboratory is based on evidence that the reactive aldehyde malondialdehyde it accumulates in neurons following repeated treatment with methamphetamine. Malondialdehdye can modify and inactivate essential proteins and enzymes, and thus may contribute to methamphetamine-induced damage to dopamine and serotonin neurons. Recent work from our laboratory shows that repeated methamphetamine treatment results in widespread increases in malondialdehyde-modified proteins in several dopamine-rich and serotonin-rich regions of rat brain. We hypothesize that malondialdehyde, in addition to inactivating essential proteins, can lead to the accumulation of other potentially toxic compounds, such as DOPAL. Little is known about the specific proteins that are modified by maldondialdehyde, or the precise role that malondialdehyde plays in methamphetamine-induced neuronal damage. Thus, further examination of malondialdehyde-induced protein modifications and neurotoxicity following repeated methamphetamine treatment is another focus of the research in my laboratory.
Current Research Grants
Title: The Role of Mu Opioid Receptor Activation in Psychostimulant-Induced Gene Expression in the Patch Compartment of Dorsal Striatum and Repetitive Behaviors.
Source: National Institutes of Health/National Institute on Drug Abuse (R15 DA025303-01A1)
PI: Kristen A. Horner, Ph.D.
Direct Costs: $150,000 (Total Award: $225,815)
Kristen A. Horner, John C. Hebbard, Anna S. Logan, Golda A. Vanchipurakel and Yamiece E. Gilbert. Activation of mu opioid receptors in the striatum differentially augments methamphetamine-induced gene expression and enhances stereotypic behavior. (2012) J Neurochem 120: 779-794.
Kristen A. Horner, Yamiece E. Gilbert and Susan D. Cline. Widespread increases in malondialdehyde immunoreactivity in dopamine-rich and dopamine-poor regions of rat brain following multiple, high doses of methamphetamine. (2011). Front Syst Neurosci 5:27-37.
- Kristen A. Horner, Yamiece E. Gilbert and Erika S. Noble. Differential regulation of 5-HT2A receptor mRNA expression following withdrawal from a chronic escalating dose regimen of D-amphetamine. (2011). Brain Research 1390: 10-20.
- Mario E. Alburges, Amanda J. Hoonakker, Kristen A. Horner, Annette E. Fleckenstein, and Glen R. Hanson. Methylphenidate alters basal ganglia neurotensin systems through dopaminergic mechanisms. (2011).Journal of Neurochemistry 117: 470-478.
- Kristen A. Horner, Yamiece E. Gilbert and Erika S. Noble. Methamphetamine-induced stereotypy correlates with patch-enhanced prodynorphin and arc mRNA expression in the rat caudate putamen: the role of mu opioid receptor activation. (2010). Pharmacol Biochem Behav 95: 910-921.
- Kristen A. Horner, Erika S. Noble and Edward C. Lauterbach. Differential regulation of prodynorphin, c-fos and serotonin transporter mRNA following withdrawal from a chronic escalating dose regimen of d-amphetamine. (2009).Synapse 63: 257-268.
- Gregory C. Hadlock, Anthony J. Baucum II, Jill L. King, Kristen A. Horner, Glen Cook, James W. Gibb, Diana G. Wilkins, Glen R. Hanson and Annette E. Fleckenstein. Mechanisms underlying methamphetamine-induced dopamine transporter complex formation. (2009). J Pharmacol Exp Ther 329: 169-174.