Tobacco Documents Online

Mr. Stevens C Meeting was adjournedat 11:55 with~agreement to schedule another session im approximately six months. "~ u~' ~, Xc: Dr. A. W. Spears Dr. H. J. Minnemeyer Dr.. S. T. Jones FJSlhsh F /J. Sc u tz~ `T

Mr. StevensC C trying.to determine the exact areas of the brain affected by nicotine using rats with cannulasimplanfied into specific brain sites through which nicotine or other drugs can be administered. He has found that the most dramatic effects are in themid-brain area which controls pleasure-pai,n sensations, motorfunetions, autonomic nervous system and respiration. He hypothesizes that for a drug to affect brain function it must mimic some naturally occurring substance in the brain im terms of its structural configur- ation. Hence naturally occurring,1-nicotine may structurally resemblethe essential part of Enkephalin. It is interesting to note that the other isomer, d-nicotine has essentially no effect on the brain in this rat test system. Various derivatives of nicotine, such as N-benzylni~cotine (suppliedby P.M.Y if administered prior to.nicotine administration, block the effect of the nicotine. Adfiinistration of nicotine to the central areaof the brain results in a 20-30 fold increase in.theEnkephali~n level in this area and belownormal levels in other areasof the brain, The significance of this observation.is not yet known~. Dr. John Kreisher, CTR staff, reported on the status of the Arylhydrocarbon hydroxylase inducability assay and reviewed the possible clinical significance of this enzymegroup. He reported that the assay is now standardized to the extent that 7 l!aboratories across the country can obtain consistent and reproducible results. Studies are underway to determine if susceptability to cancer cambe predicted by use of this assay andwhether or not inducability in one tissue (i.e. lymphocytes), is predictive of ASH inducability in other tissues (1ung, livers, skin) in thesame individual. Dr. Sheldon C. Somers, CTR staff, reported on a recent site visit to Boulder, CoLorado where several investigations funded by CTR are being carried out under Drs. Alpern, McClearn, Collinsand,others. These are.all studies involving Behavioral Genetics whereim mice of various strains are given nicotine and other drugs(alcohol, caffeine, etc.)) and observed for strain specific behavioral differences. The work is still in the fairly early stages so nodefinite results are available, but it can tie said that there.arediflferences between genetic strains in their reaction to nicotine and;other drug treatments. Dr. William Gardner (CTR) gave a very brief report on the status of twin studies. He reportedithat an attempt to set up a twin registry in theU.S.. had failed and been abandoned mainliy due tothe.wide.differences in geographical location commonly found between members of the pairs. The Swedish twin studies are continuing and a Finnish twinn registry is being established. To date 53,000 questionnaires have been received fromFinnish twins. These are much more detailed and complete tham those used in.the Swedish study. It appears that cancer deaths in Finnish.twins are 5times as high as in the Swedish group.

4 'Tor/kIle, MEMORANDUM November 23, 1977 TO: Mr. A. J. Stevens . FROM: F. J. Schultz SUBJECT: Summary of CTR Meeting 11/22/77 As.you requested, I have briefly summarized the - reports given at this meeting. Mr. Yeaman opened the meeting with a few very brief remarks of welcome and introduced Dr. Donald Fordd as.a new CTR staff member whose specialty is central nervous system (CNS), studies.. Dr. Fordexplained in a general way the structure of nervecelLs in.the brain, pointing out the various structural details and their specific functions in the transmission of nerve impulse as it is understood today. On the basis of this information he then discussed the possibTe mode or modes of action of nicotine. He stated that in some respects, nicotine action appears to parallel that of opiates although there are enough exceptions or anomalies observed to point up.the fact that.much still needs to be learned to arrive at an understanding of the mechanism. Current thinking is that opiates have an effect on the action of neuro-transmitters at the nerve junction,membranewhile nicotine affects the neuro-receptor function at the nerve junction. If this is the case,, the apparent effect of either opiates or nicotine would be similar but wouldarise through different biochemical mechanisms. Enkephalin is a recently reported pr_ptide isolated from. brain cells which when administered to animals produces effects similar to the opiates. Its true function in the brain is not yet understood,, but it is suspected to be involved in the reguSation of sensory perception (perhaps regulates paiin). C 4~ Dr. Ford's 5 recommendations for areas of work in order (.,7 of his priority are attached. ~ Abood is a CTR grantee working on studies Dr Leo G ~ . . of the mechanism of nicotine effects on the brain. He is N Ln ~ `