Linda K. Vaughn, Ph.D.,

Professor, Chair
Physiology, Neurophysiology, Neuropharmacology

Schroeder Complex 474D

(414) 288-6566

E-mail

Dr. Vaughn received her Ph.D. from the University of Michigan in 1977. She was a postdoctoral fellow at the University of Calgary. She joined the faculty at Marquette in 1979.

Research Interests:

My current research program is focused on the neuropharmacology of nitrous oxide. This is a widely used drug, both in medicine, where it is used as an adjunct for anesthesia, and in dentistry, where it is used as an analgesic and anxiolytic drug. Prolonged exposure to nitrous oxide in humans and animals can produce dependence and withdrawal signs. Past collaborative studies between our laboratory and the laboratory of Dr. Raymond Quock have contributed to the now widely accepted belief that the analgesic effects of nitrous oxide are mediated through interaction with opioid receptors and the anxiolytic effects are mediated through interaction with the GABA-A receptor. Our laboratory is now investigating the mechanisms by which nitrous oxide produces physical dependence and withdrawal signs. We have found that opioid receptors are not involved in withdrawal as they are in analgesia, but that neurotransmitter receptors that activate ligand-gated ion channels, GABA-A receptors, 5HT3 receptors and NMDA receptors are apparently involved in dependency and withdrawal. This mechanism of action corresponds closely to the action of ethanol, which also acts on these receptors, and is not similar to the action of narcotic drugs which act through opioid receptors. Both neuropharmacological and pharmacogenetic approaches have been used to identify and clarify the role of these neurotransmitter receptors in the nitrous oxide-induced dependency and withdrawal reactions.

Currently, we are using in situ hybridization techniques to examine nitrous oxide-induced alterations in the expression of GABA-A receptor subunits. We have found that nitrous oxide exposure induces increase in GABA-A receptor a1 subunit mRNA expression in the cingulate cortex, hippocampus, ventral tegmental area and medial septum of mice. These results are also consistent with the hypothesis that ethanol and nitrous oxide produce dependence and withdrawal through common mechanisms. Future studies on the effect of nitrous oxide on the full complement of subunits of the GABA-A receptor, as well as additional receptor types, are planned to provide a more complete understanding of the neuronal mechanism of action of nitrous oxide.

Selected Publications:

1. Quock RM, Vaughn LK. Nitrous oxide and endogenous opioid peptides. In Pharmacology of Opioid Peptides, ed by LF Tseng, Harwood Academic Publishers, Amsterdam, pp. 321-343, 1995.
2. Knapp RJ, Vaughn LK, Yamamura HI. Selective ligands for mu and delta opioid receptors. In Pharmacology of Opioid Peptides, ed by LF Tseng, Harwood Academic Publishers, Amsterdam, pp. 1-28, 1995.
3. Quock RM, Vaughn LK. Nitrous oxide: Mechanism of its antinociceptive action. Analgesia 1:3, 151-159, 1995.
4. Vaughn LK, Pruhs RJ. Strain dependent variability in nitrous oxide withdrawal seizure frequency. Life Sci 57, 1125-1130, 1995.
5. Quock RM, Mueller JL, Vaughn LK, Belknap JK. Nitrous oxide antinociception in BXD recombinant inbred mouse strains and identification of quantitative trait loci. Brain Research 275:23-29, 1996.
6. Quock RM, Vaughn LK. Involvement of nitric oxide in anesthetic drug effects. Pharmacoanesthesiology 10:47-50, 1997.
7. Johanek L, Cullinan WE, Vaughn LK. Increased mRNA expression for the a1 subunit of the GABAA receptor following nitrous oxide exposure in mice. Molecular Brain Research 89: 41-49, 2001.
8. Mueller JL, Ellenberger EA, Vaughn LK, Belknap JK, Quock RM. Detection and mapping of quantitative trait loci (QTLs) that determine responsiveness of mice to nitrous oxide (N2O) antinociception. Neuroscience (in press).
9. Vaughn, L.K. and R.M. Quock. Nitrous oxide and opioid receptors. In: Encyclopedic Reference of Pain by Robert F. Schmidt and William D. Willis (Editors). Springer-Verlag (in press).