Traditional approaches to the problem of drug dependence have focused upon treatment after drug dependence has been well established. A number of pharmacotherapy approaches to the treatment of drug dependence have been undertaken, and these studies have consistently produced negative results. In fact, the very drugs we propose to study in this application have been investigated as possible treatment for drug dependence. Even though these drugs are not effective in the treatment of drug dependent patients, such drugs may not be used to alter behaviors which place individuals at high risk for drug dependence. Once the drug reinforcement and associated dependence are in operation in the drug dependent individual, such drug interventions may be of little value. In the non drug dependent individual, these drugs may be effective via a totally different mechanisms. Modifying high risk behaviors, like aggression and impulsivity, may reduce the probability that the individual will engage in drug seeking prior to the development of drug dependence. Rather than attempting to interfere with the reinforcing effects of the drug of abuse the proposed research would be an initial step toward examining the possibility of reducing drug seeking by altering antecedent high risk behaviors. In this application, we propose to examine an area of research which may lead to a different approach to the treatment of drug dependence, namely the pharmacological alteration of certain classes of behavior which are associated with drug dependence and place individuals at high risk for drug dependence. These behaviors are aggression and impulsivity; taken together they contribute a """"""""temperament"""""""" which has been predictive of subsequent drug dependence, aggression and criminal behavior. We propose to examine the alteration of aggressive and impulsive behavior under controlled laboratory conditions employing drugs which have been used to treat patients with similar types of behavior problems. There is suggestive evidence that these drugs may be useful in altering behaviors which frequently lead to drug dependence. Four pharmacological agents will be used to examine their effects on aggressive and impulsive behavior in two different populations of subjects: (1) subjects with a history of childhood conduct disorder (CD) + current antisocial personality disorder (ASPD), probably the highest risk population and (2) matched controls the drug to be employed are: carbamazepine, fenfluramine, methylphenidate and paroxetine. The proposed research will provide information about the effects of selected therapeutics agents on fundamental aspects of behavior (aggression and impulsivity) which may place individuals at risk for drug dependence. Pharmacological effects of these therapeutics drugs on such behavior in a high risk population may provide information relating to alternative strategies in dealing with drug dependence.
| Pietras, Cynthia J; Cherek, Don R; Lane, Scott D et al. (2003) Effects of methylphenidate on impulsive choice in adult humans. Psychopharmacology (Berl) 170:390-8 |
| Cherek, Don R; Lane, Scott D; Pietras, Cynthia J et al. (2002) Effects of chronic paroxetine administration on measures of aggressive and impulsive responses of adult males with a history of conduct disorder. Psychopharmacology (Berl) 159:266-74 |
| Cherek, D R; Lane, S D (2001) Acute effects of D-fenfluramine on simultaneous measures of aggressive escape and impulsive responses of adult males with and without a history of conduct disorder. Psychopharmacology (Berl) 157:221-7 |
| Cherek, D R; Lane, S D (2000) Fenfluramine effects on impulsivity in a sample of adults with and without history of conduct disorder. Psychopharmacology (Berl) 152:149-56 |
| Cherek, D R; Lane, S D (1999) Effects of d,l-fenfluramine on aggressive and impulsive responding in adult males with a history of conduct disorder. Psychopharmacology (Berl) 146:473-81 |
