Linda K. Vaughn, Ph.D.,

Professor
Physiology and Neurobiology

Schroeder Complex 474D, 452

(414) 288-6566, 288-4552

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:

We investigate the interaction between cannabinoid and GABAA receptors in the control of anxiety.  In humans, marijuana produces complex effects on anxiety.  It is capable of causing both a reduction in anxiety and panic attacks.  In animals, cannabinoid compounds (marijuana-like) also cause complex effects, but, in general, they cause a reduction in anxiety at low doses and increases in anxiety at high doses.  The brain makes its own endogenous cannabinoids which act on cannabinoid receptors.  There are two well characterized cannabinoid receptors, the CB1 and CB2 receptors.  The predominant receptor in the brain is the CB1 receptor.  Endogenous cannabinoids – or endocannabinoids – act as unconventional neurotransmitters in that they are lipids and act through retrograde signaling.  They are produced by the postsynaptic neuron, diffuse to CB1 receptors located on the presynaptic neuron, and inhibit the release of neurotransmitter.  CB1 receptors are primarily located on the terminals of GABA and glutamate neurons.  The fact that exogenously administered cannabinoid compounds can bind to receptors on both excitatory (glutamate) and inhibitory (GABA) neurons partially explains their complex and contradictory effects on anxiety.  We would like to study the interaction between cannabinoids and the GABA system by investigating the anxiolytic effects of cannabinoids while pharmacologically manipulating the activity of specific GABAA receptors that contain selected alpha subunits.  We will test the effects of both exogenously administered cannabinoid agonists as well as manipulating levels of endogenous cannabinoids.  The alpha subunit of the GABAA receptors is thought to be important in determining responsiveness to anxiolytic compounds, but whether the cannabinoid receptors are acting on GABAergic neurons that innervate these receptors is unkown. The brain region where cannabinoids are thought to exert their anxiolytic actions is also unknown and since there are known regional distributions of various alpha subunits, determining the subunit composition of the relevant GABAA receptors could provide evidence regarding potential sites of action.  Determining the pharmacological and anatomical characteristics of the GABAA receptors that are affected by cannabinoids will help understand the neurobiology and control of anxiety.

 

Selected Publications:

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, Berlin Heidelberg New York, pp. 1347-1349, 2007 (invited review).

 

Quock, RM, Vaughn LK. Do inhalation general anesthetic drugs induce the neuronal release of endogenous opioid peptides? Life Sci 77: 2603-2610, 2005.

 

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 123: 743-749, 2004.

 

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.

 

Quock RM, Vaughn LK. Involvement of nitric oxide in anesthetic drug effects. Pharmacoanesthesiology 10:47-50, 1997.

 

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.

 

Vaughn LK, Pruhs RJ. Strain dependent variability in nitrous oxide withdrawal seizure frequency. Life Sci 57, 1125-1130, 1995.

 

Quock RM, Vaughn LK. Nitrous oxide: Mechanism of its antinociceptive action. Analgesia 1:3, 151-159, 1995.

 

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.

 

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.