26 



Mr. DeNoble. Can I walk over there, or is that hard to do? 



Mr. Waxman. That's going to be a little difficult to get this on 

 the microphone. 



Mr. DeNoble. That would be fine. 



If you look at what's called fixed ratio size, that is how many 

 times a rat has to press a lever. And if you look at the unit number 

 1, he gets a single press, he gets a single injection. If you now say 

 to the animal, I'm going to see how hard you'll work for it, I'm 

 going to ask you to press the lever twice. The animal 



Mr. DeNoble. Thank you. This represents an animal pressing 

 the lever twice for nicotine. What is interesting is this dotted line 

 tells you how many infusions the animal is taking. Here he is tak- 

 ing a stable level of infusions, if you ask him to double his work 

 output. 



You can ask him to triple it, quadruple it, et cetera. The animals 

 will continue to work and press the lever to get nicotine, up to 

 about a fixed ratio of about 6 or 7, and then it begins to fall off. 

 The cost is just too high. 



Two points about this slide. One is, animals will work for nico- 

 tine; and second is, animals will maintain a constant level of nico- 

 tine infusion over different work schedules. 



Mr. Waxman. At our April 14th hearing, Philip Morris' chief ex- 

 ecutive officer testified that you had, quote, "Concluded that nico- 

 tine is a reinforcer in the class of non-addictive chemical com- 

 pounds such as saccharine and water." We asked Philip Morris for 

 these and other relevant documents, but they were unable to pro- 

 vide them prior to this hearing. 



Is Philip Morris correct that you concluded after you did this 

 work, that nicotine is a reinforcer comparable to saccharine and 

 water? 



Mr. DeNoble. No, not at all. 



Mr. Waxman. What would be the difference? 



Mr. DeNoble. Well, water is a reinforcer, but you need to be 

 food-deprived or very nervous to drink it. Food is a reinforcing 

 agent, but you need to be hungry, or it needs to taste good, it re- 

 quires tongue. 



Nicotine was being injected directly into the vein. We went on to 

 use a series of blocking agents to show that it was the brain activ- 

 ity of nicotine, not its effect on the periphery, not its effect on taste 

 systems, that would determine its reinforcing effects. An animal 

 doesn't have to need nicotine for it to be a reinforcer. All it has to 

 do is experience it. 



Mr. Waxman. Now, you said, "food." Would that also apply to 

 saccharine, that you need the taste of the saccharine? 



Mr. DeNoble. Exactly. Yes, the reinforcing effects of saccharine 

 are clearly mediated via its interactions with the taste system in 

 the mouth. 



Mr. Waxman. Now, if you ran the kind of tests you did for nico- 

 tine on saccharine, what would you find? 



Mr. DeNoble. Saccharine is not self-administrated intra- 

 venously, to the best of my knowledge. 



Mr. Waxman. So you have an intravenous feeding of this nicotine 

 that's going right to the brain. If you put saccharine intravenously, 



