Linda K. Vaughn, Ph.D. Research Lab
We investigate the endogenous cannabinoid (marijuana-like) system. The brain makes its own endogenous cannabinoids which interact with cannabinoid receptors to cause effects on a number of physiological systems including anxiety and mood, control of food intake, learning and memory, reward and addiction, stress, analgesia and temperature regulation. We are particularly interested in three aspects of cannabinoid physiology.
- The role of endocannabinoids in stress-induced relapse to cocaine seeking behavior. There is strong evidence that relapse to drug taking can be triggered by exposure to stress. The goal of this research project is to understand the mechanisms by which stress triggers relapse. Our approach is to use a preclinical mouse model of cocaine abuse and relapse in which stress-induced relapse is assessed according to the ability of brief exposure to a stressful stimulus to re-establish preference for a distinctive environment previously associated with cocaine reward after a period of drug abstinence/extinction. We have found that blockade of the CB1 cannabinoid receptor can effectively block stress induced reinstatement of previously established cocaine conditioned place preference in mice, suggesting that the use of cannabinoid antagonists may be an effective pharmacological tool to dampen the effects of stress to enhance return to drug seeking behavior. Our goal in this project is to advance the potential development of pharmacological tools by more firmly establishing the role of endogenous cannabinoid receptor signaling (ECS) in stress-induced reinstatement.
- The role of endocannabinoids in anxiety. Approximately 40 million American adults ages 18 and older, in a given year, have an anxiety disorder. The neurobiology of anxiety, however, is not well understood. 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. Using a well known mouse model of anxiety, the elevated plus maze, we have found that antagonism of a specific type of GABAA receptor inhibits the anti-anxiety effect of cannabinoid drugs. Our goal is to further characterize the interaction between the endocannabinoid system and these GABAA receptors. We believe that understanding this interaction may lead to a better understanding of the neurobiology of anxiety and more selective pharmacological treatments.
- Interaction between the endocannabinoid system and nitrous oxide – the role of endocannabinoids in analgesia. Our laboratory has been studying the role of nitrous oxide in analgesia and anxiety as well as the neurobiology of nitrous oxide withdrawal seizures for several years. Nitrous oxide has well known analgesic effects, effects that are largely mediated by interaction with the opioid system and which involve the retrograde transmitter nitric oxide. We have preliminary data that a cannabinoid antagonist can reduce the analgesic effect of nitrous oxide. Since the endocannabinoid system also acts as a retrograde messenger, interacts with the opioid system, and has analgesic effects, studying the interaction between these two systems may help us understand the neuronal control of pain pathways.
- Vaughn LK, Mantsch JR, Vranjkovic O, Stroh G, Lacourt M, Kreutter M, Hillard CJ Cannabinoid receptor involvement in stress-induced cocaine reinstatement: potential interaction with noradrenergic pathways. Neuroscience. 2012 Mar 1;204:117-24. Epub 2011 Aug 16
- Vaughn LK, Quock RM, Nitrous oxide antinociception and endogenous opioid peptides. Encyclopedic Reference of Pain (invited review), (in press).
- Vaughn LK, Denning G, Stuhr K, de Wit H, Hill M, Hillard CJ, Endocannabinoid signalling: Has it got rhythm? Br J Pharmacol 160:530-543, 2010.
- Vaughn, L.K. and R.M. Quock, Nitrous oxide and opioid receptors. 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. 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. Pharmacology of Opioid Peptides, ed by LF Tseng, Harwood Academic Publishers, Amsterdam, pp. 321-343, 1995.