23 



Mr. DeNoble. Yes. That is a poster, and this is a rat that would 

 be inside of an experimental chamber and has a switch, what I 

 refer to as a lever. The rat is also, you can see on his back he is 

 surgically prepared with a catheter that lodges in his vein or the 

 atrium of the heart. The rat has the option to go over and press 

 the lever. 



When he does, it activates some programming circuitry, you 

 record when the press occurred. It also activates an infusion pump, 

 and that pump then will infuse nicotine, or whatever solution you 

 have, into the animal's vein. Again, if that solution is a reinforcer, 

 the rat will continue to press the lever at reasonably high rates. 



Mr. Waxman. We have another poster, which would be Exhibit 

 9. 



That shows the number of times the rats press the lever for nico- 

 tine. Can you explain it for us? And let me indicate, by the way, 

 that both of these posters are furnished to us from your slides that 

 were given to us by you? 



Mr. DeNoble. That's correct. 



This is a grouped data shot. Primarily, after the rats are sur- 

 gically prepared with the catheter, you put them in the box and 

 they are hooked up to a pump which has saline in it. And the ani- 

 mals don't press the lever very often for saline. If fact, they pressed 

 it less than 12 times. 



If you now substitute nicotine at a dose of 32 micrograms per 

 kilograms, you can see that after several days an animal will inject 

 itself well over — almost 90 times per 24-hour session. If you now 

 remove the drug solution, in this case nicotine, the animal stops 

 pressing the lever in a series of days. So the nicotine self-adminis- 

 tration falls back down to the original saline levels. 



Standard control is to reintroduce the nicotine. And that is the 

 second large bar where you see it says "32." And that is, again, 

 where the animals will resume pressing the lever, once nicotine is 

 again made available intravenously. 



Mr. Waxman. How did you pick the dose of nicotine to give to 

 the rats? 



Mr. DeNoble. Well, we looked through the literature at the 

 time, in the early 1980's. And it was determined by us that about 

 1 to 2 milligrams of nicotine was coming through in a cigarette. I 

 just simply divided that by a 70 kilogram individual and came up 

 with 30 micrograms per kilogram. 



Mr. Waxman. And is that any relationship to what a human 

 would get? 



Mr. DeNoble. It's basically — it's very difficult to answer that 

 question. It's based upon what a single cigarette delivers to a 

 human, but I don't know if it's any relationship to the physiological 

 effects. I cannot answer that. 



Mr. Waxman. We have the next exhibit. Exhibit 10. It's a little 

 bit more complicated. It's my understanding that it shows how 

 hard the rats will work for nicotine. Can you explain that to us? 



[Exhibits 9 and 10 follow:] 



