Association between behavioral regulation and cocaine cue preference
This project will study animal models of five psychological traits (sensation seeking, inattention, impulsivity, habituation, and the attribution of incentive salience) thought to underlie behavioral regulation and to be related to drug abuse. Some or all of these psychological traits are thought to predispose individuals to drug addiction. The relationship of these traits to each other and the degree to which the traits, both individually and together, predict cocaine cue preference will be determined. The genetic basis of these psychological traits will be determined in conjunction with Core C. We have phenotyped 1600 male and female N/NIH heterogeneous stock (HS) rats using 6 behavioral tasks, and we plan to phenotype 1600 additional rats to increase statistical power of the study. Each rat is tested using locomotor response to novelty, light reinforcement, delay discounting, choice reaction time, and Pavlovian conditioned approach. 1600 rats from prior funding period were also tested for cocaine conditioned cue preference. Individual differences in the behavioral phenotypes and psychological traits will be used to perform a statistically sophisticated latent trait analysis to investigate how the behavioral phenotypes and psychological traits are related to each other and to cocaine cue preference. These data is also used for a genome wide association study (GWAS) to determine the genetic basis of these traits (Core C). Upon completion of Project 3, we will have an in-depth understanding of the relationships between the behavioral phenotypes, psychological traits and cocaine conditioned cue preference. The results of the analysis, which may be different for each sex, will be reviewed with the goal of determining how well the psychological traits predict cocaine cue preference and more generally their contribution to an overall model of behavioral regulation.
Methods for genotype
1) Genotypes were generated as described in [PMID: 23979941, DOI: 10.1534/g3.113.007948] 2) low-coverage WGS based on Riptide library preparation (pulication in progress)
Methods for Phenotypes
Locomotor ResponseLocomotor Response to a novel environment is recorded using infrared motion-response system (Hamilton-Kinder) which records beam interruption.
Delay DiscountingDelay Discounting was measured using a sequential patch depletion procedure. This procedure mimics naturally occurring choice problems confronting animals while foraging in a patchy environments (i.e., travel delays and patch depletion).
Light ReinforcementLight Reinforcement. Rats show an increase over their normal operant level of bar pressing in a dark box if dim light onset is made contingent upon this response. Demonstration of the light reinforcement protocol.
Reaction Time Reaction time protocol is used to measure attention and impulsivity, as well as habituation and sensitization. Demonstration of the reaction time protocol.
Social ReinforcementSocial Reinforcement is an important class of sensory reinforcers. We have developed an procedure and an automated apparatus to measure social approach responses. In addition, the social reinforcement monitor can be used for studies of responding for social reinforcers, light reinforcers, liquid food reinforcers, self-administered drug reinforcers and the interaction between them.
Enriched Environment Enriched Environment for rats was used in a pilot project “Effect of enrichment/deprivation on drug abuse related endophenotypes”.
Pavlovian Conditioned ApproachPavlovian Conditioned Approach will be used to classify rats as sign-trackers (those that attribute incentive salience to reward cues) and goal-trackers (those that assign only predictive value to reward cues).
Methods for Omics