Neuropeptides and Drugs of Abuse

United States

Sponsor: Rao S. Rapaka, CPSRB, DNBR, NIDA

Meeting Summary

This symposium was arranged as a satellite meeting to the "Summer Neuropeptide Conference", an annual International Meeting co-funded by NIDA. The Keynote Speaker was Dr. Tomas Hokfelt and he gave an overview on neuropeptides, in general and specifically addressed present issues on selected peptides. The conference was organized as four sessions and, at the end, an extensive discussion forum was organized.

The first session was mainly on neuropeptide processing and related enzymology. Three talks were presented: Dr. Beinfeld on CCK biosynthesis and role of CCK in psychostimulant sensitization, Dr. Mains on Kalirin, axon and dendrite initiation and maintenance and Dr. Fricker on new insights on neuropeptide processing and lessons learnt from past experiences in this area.

The second session had seven speakers. Dr. Heinricher gave a presentation on nociceptin and the mechanisms involved in analgesia. Dr. Heinrciher presented evidence to recommend that a circuit-level approach is likely to be required if we are to understand the contribution of this peptide to physiology and behavior. Dr. Payza presented minireview on FMRF amide related peptides and their role in pain and Dr. Angulo spoke on the mechanisms of methamphetamine-induced toxicity and the role of neurokinin-1 receptor. Two more talks on pain were given by Drs. Zadina (endomorphins) and Porreca (dynorphin). Dr. Morilak gave a talk on interaction between galanin and norepinephrine in the response to stress.

The third session had six speakers. Dr. Deutch presented his talk on dopamine and neurotensin interactions and Dr. Rostene gave nice minireview on neurotensin and proposed that neurotensin receptor antagonists, by reducing the effects of psychostimulants, may have potential clinical implications in the treatment of drug abuse. Dr. Richelson also gave a talk on neurotensins and suggested that neurotensin receptor agonists, such as NT69L, may be explored as treatment for nicotine and other psychostimulant abuse. There were two talks on NPY. Dr. Mullins gave a brief overview on NPY receptor subtypes and its regulation of physiological activities including food intake and energy expenditure, vasoconstriction, ethanol sensitivity and consumption, nociception, depression and Dr. Kaskow presented his talk on possible mechanisms for CRH-NPY interactions in regulating anxiety behavior. Dr. Kuhar spoke on CART biosynthesis and CART peptides and stated that there are two important gaps: discovery of CART receptors and, synthesis of small molecule CART agonists and antagonists.

The fourth session had several talks on ligand design and high throughput screening using chemical libraries. Dr. Sarnyai gave a minireview of the role of CRH factor in cocaine addiction and suggestions on developing therapies. Dr. Rivier discussed on the medicinal chemistry of CRF ligands and their potential in treating stress disorders. Dr. DeLeone gave a brief overview of orexins and MCH hormone and their role in addiction and other behavioral activities. There were three talks in the design of opioid ligands; Dr. Hruby presented his talk on design of chimeric peptides that interact with two receptors to produce the desired biological activity, such as, ligands that have opioid agonist activity and CCK antagonist activity, Dr. Schiller on his recently published method on developing opioid antagonists and Dr. Carroll on development of ligands for opioid receptors and monoamine transporters. Dr. Houghten's talk was on the different libraries and their potential for discovering novel ligands. Dr. Houghten presented several examples of new molecules that were discovered using this technique. Dr. Mierke spoke on receptor-ligand binding for GPCRs using nuclear magnetic resonance.

The last session was a discussion session, where several new ideas were proposed that will help in promoting neuropeptide research at NIDA. There was a strong feeling among the participants that there should be a RFA on neuropeptides and drugs of abuse. Another important recommendation is that NIDA should take a lead in supplying neuropeptides, labeled peptides and nonpeptide neuropeptide ligands to the research community. The attendees felt as NIDA's track record in drug supply is superb and as NIDA already supplies a number of opioid ligands, this would be an excellent service to add on to their current activity. The attendees recommended that the proceedings be published. Dr. Frank Porreca agreed to look into the publication of the proceedings.