New York, continually reviewed our research and approved our re- 

 search. Senior management also reviewed and made final decisions 

 determining whether data could be published, presented at sci- 

 entific meetings, or even discussed in the scientific community. 



With regard to the Philip Morris press release, dated March 31st, 

 1994, the statements made concerning my research and my assess- 

 ment of the self-administration experiments are out of context and 

 misleading. Further, during my employment with Philip Morris, 

 three manuscripts were approved for publication. Two of these 

 manuscripts were subsequently ordered to be withdrawn by the 

 company after this approval. 



In addition, a 1983 scheduled presentation of the nicotine self-ad- 

 ministration paper at the American Psychological Association meet- 

 ing was also blocked by the company. Finally, without prior discus- 

 sion or prior warning, the behavioral pharmacology laboratory was 

 abruptly closed in April of 1984. 



Mr. Chairman, and members of the committee, I would like to 

 thank you for reading our statement, and I welcome any questions. 



[The prepared statement of Dr. DeNoble follows:] 



Statement of Victor John DeNoble 



Mr. Chairman and members of the committee, I am Dr. Victor John DeNoble, a 

 behavioral psychologist, and I am senior behavior analyst for the Community Men- 

 ted Retardation Program for the State of Delaware. I am grateful to have this oppor- 

 tunity to discuss my research at this hearing on tobacco. 



From 1980 to 1984, I was employed at the Philip Morris Research Center in Rich- 

 mond, Virginia as an associate senior scientist. My responsibilities were to establish 

 and direct a behavioral pharmacology laboratory to study the behavioral and physio- 

 logical effects of nicotine and other smoke components in rats. Our initial goal was 

 to identify the behavioral effects of nicotine on the central nervous system and to 

 establish structure activity relationships among organically synthesized nicotine 

 analogues. The purpose of the nicotine analogue program was to develop an ana- 

 logue that would retain physiological and behavioral effects in the brain and be de- 

 void of any pharmacological effects in other organs, specifically, the cardiovascular 

 system. In order to accomplish this goal, a characterization of the behavioral effects 

 of nicotine in rats using a variety of operant conditioning procedures needed to be 

 developed. 



With regard to the nicotine analogue program, our primary behavioral test was 

 a nicotine drug discrimination procedure. Rats were trained to identify whether they 

 had been injected with nicotine or saline. Using nicotinic-cholinergic antagonists, we 

 demonstrated that the rats ability to discriminate (identify) whether it was injected 

 with nicotine or saline was mediated by nicotine's effect in the brain not by nico- 

 tine's effect on the peripheral nicotinic receptors. 



This test procedure was used to identify nicotine analogues that would mimic the 

 effects of nicotine in this discrimination procedure. This behavioral data was then 

 combined with nicotinic receptor binding data, as well as peripheral pharmacology 

 data generated outside Philip Morris Research Center to develop structure-activity 

 relationships among these analogues. The goal of this program was to identity a nic- 

 otine analogue that would have central nervous system effects without effects on the 

 cardiovasciilar system. 



In our self-administration studies we demonstrated that: (1) nicotine functioned 

 as an intravenously delivered reinforcer for rats; (2) that rats would press levers 

 several times for a single injection; (3) that nicotine self-administration was con- 

 trolled, at least in part, by nicotine levels in blood or tissue; (4) that the reinforcing 

 effects were mediated by central nicotinic-cholinergic receptors; (5) that endogenous 

 opioid receptors did not mediate nicotine's reinforcing effects and, finally; (6) that 

 termination of chronic self-administration of nicotine over several weeks did not re- 

 sult in observable behavioral signs of a physiological dependence. 



With regard to this last observation, we extended our findings by examining the 

 effects of nicotine self-administration on concurrent lever pressing maintained by 

 food. Concurrent nicotine self-administration was shown not to interfere with lever 

 pressing for food and that discontinuing access to nicotine self-administration did 



