The primary objective of the proposed research is to adapt three procedures that we are currently using to measure impulsive behavior in rats to mice and to standardize these procedures in mice using parametric and pharmacological manipulations. The first task measures impulsivity in terms of the ability of animals to wait, using a differential schedule of low rate (DRL) schedule. This task requires the animal to wait between responses to earn a reward. The second behavioral procedure measures impulsivity by assessing the value of delayed rewards. This task measures how much the animals value delayed and/or probabilistic rewards using an Adjusting Amount (AdjAmt) procedure. The third procedure measures impulsivity in terms of the ability to stop (inhibit) an ongoing prepotent response. Greater impulsivity is indicated by slower stop reaction times. All three of these procedures have been used to characterize behavioral processes that may underlie impulsive behavior in both rats and humans. We plan to characterize performance on these tasks in two inbred strains of mice, which have been widely used as background strains for the development of transgenic models, and have been shown to exhibit pronounced differences in behavior. The effects of drugs will be tested in the two strains of mice and compared to results we have previously observed in rats in order to test cross species validity of the tasks. A major goal of the proposed studies is to establish and characterize these three test procedures in mice, so that the procedures can be used in future studies to identify the genetic basis of individual differences in performance and drug effects on impulsive behavior. The behavioral tasks to be developed in this project with mice are parallel to existing tasks used with humans and rats. Related studies are ongoing in other projects using humans and rats. The results of the mouse, rat and human studies will be compared to examine concordance in the behavioral processes and to assess the validity of the rat models to human behavior. The proposed studies with mice will allow us to extend our investigation to the genetic basis of impulsive behavior.
|Krall, C M; Richards, J B; Rabin, R A et al. (2008) Marked decrease of LSD-induced stimulus control in serotonin transporter knockout mice. Pharmacol Biochem Behav 88:349-57|
|Winter, J C; Kieres, A K; Zimmerman, M D et al. (2005) The stimulus properties of LSD in C57BL/6 mice. Pharmacol Biochem Behav 81:830-7|