Bowles Center Researcher Receives K01 Award to Study Ethanol’s Discriminative Stimulus Effects
Joyce Besheer, Ph.D., Research Assistant Professor at the Bowles Center for Alcohol Studies, recently received a K01 Award titled, ‘Novel Mechanisms of Ethanol Discrimination.’ The 5-year project began in June 2006 and examines the role of metabotropic glutamate receptors (mGluRs) in ethanol’s discriminative stimulus effects.
All drugs of abuse share the common attribute that they produce subjective stimulus effects in humans. An example would be the feeling of “drunkenness” that accompanies alcohol drinking. These subjective effects contribute to drug taking behavior. mGluRs have been shown to influence GABA and glutamate functioning which are major components of ethanol’s stimulus properties. Besheer and colleagues are presently testing the hypothesis that mGluR5 and mGluR2/3 can moduate ethanol discrimination by interaction with GABAA and NMDA receptor systems. To accomplish this goal, behavioral phamacology techniques are being used to determine if an antagonist of mGluR5 and an agonist of mGluR2/3 will modulate ethanol discrimination and the ethanol-like stimulus properties of GABAA positive modulators and NMDA antagonists.
Dual-label immunohistochemistry with confocal visualization will be used to evaluate if mGluR5 and mGluR2/3 are co-expressed with GABAA and NMDA receptor subunits in ethanol discrimination trained rats. Fos-like immunoreactivity will be used to assess brain regional involvement in ethanol discrimination and in mGluR5 and mGluR2/3 modulation of ethanol discrimination, as well as ethanol substitutes (diazepam and MK-801). Lastly, microinjection techniques will be used to assess the functional involvement of specific brain regions in mGluR modulation of ethanol discrimination. Understanding these mechanisms is important to basic science and has numerous implications for development of therapeutic interventions in alcoholism, especially given that the discriminative stimulus properties of drugs can be important determinants of abuse liability.
Besheer has been with the Center for Alcohol Studies since July of 2002. She completed undergraduate studies at Indiana University, Bloomington, and received her Master and Doctorate degrees from the University of Nebraska, Lincoln. Her research interests include the neurobiological mechanisms underlying alcoholism and addiction, the stimulus properties of ethanol, and the neurobiology of ethanol reinforcement using animal models of ethanol self-administration.