27 



there would be no taste, there would be no reason why they would 

 want to go back to it? 



Mr. DeNoble. I don't know of any experiment that has ever 

 demonstrated that, no. 



Mr. Waxman. Finally, I want to ask you about a statement in the 

 1983 version of your unpublished article on self-administration that 

 doesn't appear in your 1986 version. In the 1983 version of the arti- 

 cle, you state that nicotine "May be a weak reinforcing agent." 

 What was the basis for this statement, and why did you take it out 

 in the later version of the article? 



Mr. DeNoble. In the earlier version of the article, I was doing 

 some literature comparisons between nicotine and other intra- 

 venously delivered reinforcers, specifically, psychostimulants like 

 cocaine and amphetamine. And if you look at just how hard an ani- 

 mal will work for these substances, nicotine looks like a weak 

 reinforcer. And I had made that statement that I thought that was 

 a fair assessment at that time. 



As we began to think and know more about the reinforcing ef- 

 fects of these drugs, we also found that rat models do not nec- 

 essarily predict how reinforcing something will be in a human. For 

 example, alcohol is not a very good intravenously delivered 

 reinforcer in rats. But alcohol is a very powerful reinforcing agent 

 in humans. So I did not put that in the second article, simply be- 

 cause I didn't think my data was strong enough to make that state- 

 ment. 



Mr. Waxman. Put this all in a historical context for us. Your 

 work on nicotine at Philip Morris, what significance did it have at 

 that time frame, and how should we view this research project? 



Mr. DeNoble. The work that we did with nicotine was clearly 

 some years ahead of the external scientific community. It wasn't 

 until 1989 that Bill Corgal demonstrated that nicotine would func- 

 tion as an intravenously delivered reinforcer for rats using the 

 same models that I used, that Paul and I used. 



Interestingly enough, he found the same dosing schedules to be 

 effective. The work that we did on self-administration, on depend- 

 ence, on tolerance, on frustration, clearly would have moved the 

 scientific community much further than it had been moved by that 

 work not getting out. 



Mr. Waxman. Dr. Mele, do you want to add anything to this? 



Mr. Mele. Just that this work, some of these studies were the 

 first to be done with nicotine. I have no doubt that other people 

 would have performed these studies subsequently, just as has been 

 done recently in Toronto, but they weren't being done at the time. 



And to quote a recent review article in Science, a news story, it 

 said that, basically, it took 6 or 7 years for the nicotine self-admin- 

 istration model to be developed and come out, whereas, it would 

 have been out much earlier had this work been allowed to go out 

 and stay out. 



Mr. Waxman. So your work at Philip Morris indicated the rein- 

 forcing nature of nicotine, information that didn't come out until 

 years later and led to the Surgeon General's Report, I guess it was 

 1988 or 1989, where the public was finally informed by the chief 

 medical officer of this country that nicotine is an addictive sub- 

 stance in cigarettes. 



