Frans van Haaren, PhD, BCBA - US grants

Cocaine abuse is one of the most important problems facing American society today. Recent years have seen a steady stream of research reports documenting the effects of behaviorally active doses of cocaine, both after acute and chronic administration. However, most of the behavioral effects of cocaine have been established in male subjects only. Relatively little research effort has been directed at investigating the behavioral effects of acute and repeated cocaine administration in females, despite the fact that evidence is available to suggest that gonadal hormones may differentially affect the behavioral effects of psychomotor stimulants, including cocaine. The long-term objective of this proposal is to analyze the role of endogenous gonadal hormones in modifying the behavioral effects of acute and repeated cocaine administration in male and female rats. It is important to identify the way in which gonadal hormones modify the behavioral effects of acute and repeated cocaine administration because of the fact that this information may be essential to the design of proper (gender-dependent) treatment and prevention strategies. Specific attention will be paid to the behavioral effects of relatively small doses of acute cocaine administration on voluntary behavior maintained by different schedules of reinforcement. Because of the fact that repeated cocaine administration may result in behavioral tolerance or sensitization to the effects of subsequent cocaine intake, schedule-controlled behavior of intact and gonadectomized male and female rats will be investigated after repeated cocaine exposure. The discriminate-stimulus properties of cocaine will also be examined in an attempt to identify some of the variables which may be responsible for cocaine's differential effects on behavior in male and female rats. Finally, the behavioral effects of withdrawal from repeated cocaine administration will be analyzed to shed more light on the variables which maintain 'drug seeking' after repeated cocaine administration, in male and female rats.

DESCRIPTION: Women constitute approximately one-third of those identified as alcohol-abusing or alcohol-dependent individuals in the United States. Why excessive alcohol consumption may arise as an activity preferred over other activities has been the subject of extensive experimental scrutiny over the past several decades. Alcohol-preferring and alcohol-nonpreferring rodent lines are now available to study genetic contributions to excessive alcohol consumption. Behavioral models have been developed to identify environmental variables which may facilitate or impede the initiation and long-term maintenance of alcohol self-administration. However, most of the paradigms used to investigate the role of these variables in the development of excessive alcohol consumption have involved male subjects only despite the fact that some evidence is available to suggest that alcohol self-administration and the behavioral and physiological effects of alcohol consumption may be gender-dependent. The present experiments are designed to study gender differences in alcohol-seeking behavior in a continuous access situation that shares many characteristics with situations in which humans consume excessive amounts of alcohol. The continuous access situation also offers the opportunity to systematically study alcohol-seeking behavior as a function of the female estrus cycle. The information obtained in these experiments will be an important first step to guide the development of appropriate, gender-dependent, alcohol abuse prevention and treatment strategies.

Impulsivity has been thought of as leading to or being the result of prolonged drug abuse (cocaine and alcohol addiction, gambling). Others have suggested that prolonged (prenatal) exposure to environmental toxicants (lead, for instance) may result in impulsive behavior, which may then facilitate further drug abuse, or hamper 'normal' development. Thus, impulsivity is an important behavioral phenomenon the etiology of which is currently poorly understood, as it has not received much experimental attention up until recently. Therefore, it is timely to consider the different methods used to study impulsive behavior and to understand the strengths and limitations of each. Both animal models and applications in the human behavioral laboratory need to be carefully scrutinized. The proposed symposium offers a framework within which this will be accomplished. All participants are actively involved in the study of impulsive behavior either in the animal laboratory or in applied settings. Dr. Evenden will discuss his pioneering work on the role of 5-HT in impulsive behavior and his interest in genetic factors that may modulate drug effects on impulsive behavior. Dr. Richards developed the innovative experimental paradigms to study indifference in experimental animals, including humans. Dr. Brockel will discuss her work on in toxicant exposure that may lead to changes in attention and impulsive behavior. Dr. van Haaren will address sex differences in the areas of impulsivity and self-control. Dr. Chelonis will contribute his work aimed at validating animal models of impulsive behavior in clinical settings. Dr. Bickel will share his expertise with respect to the application of animal models to research settings in which impulsivity can be assessed in drug-dependent human subjects. The symposium will take place at the annual meeting of the Behavioral Toxicology Society (June 25 and 26, 2000) in Palm Beach. FL.