Plenary Lecture

Plenary Lecture

Recent Advances in mGluR5 Receptor Ligands as Potential Treatments for Drug Addiction

Assistant Professor M. Foster Olive
Center for Drug and Alcohol Programs
Department of Psychiatry and Behavioral Sciences
Medical University of South Carolina
67 President Street. MSC 861
Charleston, SC 29425

Abstract: The type 5 metabotropic glutamate receptor (mGluR5) plays a pivotal role in mediating drug self-administration and drug-seeking behavior. Mice lacking mGluR5 receptors do not self-administer cocaine and are indifferent to its locomotor stimulant effects, and studies conducted by our laboratory and others have shown that mGluR5 receptor antagonists reduce self-administration of alcohol, nicotine, cocaine, heroin, and methamphetamine in rats and/or mice. mGluR5 receptor antagonists also prevent reinstatement of drug-seeking behavior elicited by drug priming or exposure to drug-associated cues, suggesting that these compounds may aid in the prevention of relapse. In contrast, recent studies from our laboratory have shown that positive allosteric modulators (PAMs) of mGluR5 receptors, which increase the activity of the receptor in the presence of glutamate, facilitate the extinction of drug-seeking behavior. We propose that this effect is due to the well-known biochemical cross-talk between mGluR5 and NMDA receptors, and that mGluR5 PAMs facilitate extinction learning as well as other forms of behavioral and synaptic plasticity. Current studies in our laboratory are being conducted to assess the role of adult hippocampal neurogenesis in the facilitation of extinction learning by mGluR5 PAMs. In summary, mGluR5 receptor antagonists may help reduce on-going drug self-administration or aid in the prevention of relapse, while mGluR5 PAMs may aid in the facilitation of extinction learning, perhaps by reducing the salience of drug-associated cues and contextual memories. Several mGluR5 antagonists are currently in clinical trials for the treatment of other medical conditions such as Fragile X Syndrome, migraine, depression, anxiety, and gastroesophageal reflux disease, and mGluR5 PAMs are in development for the treatment of schizophrenia. Eventual approval of these compounds by regulatory agencies will allow for clinical assessment of the potential anti-addictive effects of mGluR5 antagonists as well as the potential pro-cognitive effects of mGluR5 PAMs in facilitating extinction learning.

Brief Biography of the Speaker:
Dr. Olive received his B. A. Degree in Psychology from the University of California at San Diego, and his Ph.D. Degree in Neuroscience from the University of California at Los Angeles. Currently, Dr. Olive performs his research activity in the Department of Psychiatry and Behavioral Sciences at the Medical University of South Carolina. Dr. Olive's research involves the study of the role of glutamate neurotransmission in addiction using rodents models, as well as preclinical development of new glutamate-based therapeutics for treatment of drug addiction and alcoholism. This research activity is carried out in collaboration with universities in the United States and abroad. Dr. Olive is author of over 60 publications related to the field of drug addiction which are published in International Scientific Journals, books and proceedings of scientific meetings.

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