# Center for Genetic Studies of Drug Abuse in Outbred Rats

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $330,289

## Abstract

PROJECT SUMMARY/ABSTRACT
While many individuals are exposed to addictive drugs in their lifetimes, only a small percentage develop the
patterns of drug-taking associated with addiction. It is therefore crucial to identify the genetic vulnerability
factors that influence the transition from recreational to problematic drug use. Studies investigating the genetic
basis of addiction often use rodent self-administration models to induce addiction-like symptoms. However,
these paradigms differ in the patterns of drug-taking they produce. For example, in the long access (LgA)
paradigm, rats self-administer a drug such as cocaine continuously for 6 hours or longer, and this paradigm
produces escalation in drug intake over several sessions in a manner that is characteristic of addiction. In
contrast, in the intermittent access (IntA) paradigm, rats' access to cocaine is restricted such that overall intake
is limited, yet leads to “spiking” brain levels of cocaine thought to be characteristic of drug-taking during binges
in humans. Despite the lower level of intake relative to LgA, IntA results in larger increases in the motivational
value of cocaine, as indicated by increases in the effort expended to acquire the drug, and relapse to drug-
seeking after periods of abstinence.
Thus, the scientific premise of this proposal is that the behavioral and neurogenetic processes driving drug-
taking in these models are distinct, and comparing these processes in IntA versus LgA enable the dissociation
of genes that promote escalation of intake from those that induced enhanced cocaine motivation (i.e., incentive
sensitization). However, to date no studies have examined the genetic substrates of cocaine self-
administration during the IntA paradigm, and no studies have compared transcriptomic changes induced by
LgA and IntA.
To fill these knowledge gaps and identify potentially therapeutic targets, we will conduct a genome-wide
association study (GWAS) to determine the genetic variants that influence cocaine intake during IntA, and the
degree to which IntA causes incentive sensitization, as measured by changes in progressive ratio breakpoint
and cocaine self-administration despite negative consequences (footshock). Further, a unique feature of this
application is that we have carefully designed our procedure to parallel an ongoing GWAS (U01DA043799)
being conducted by Drs. Olivier George and Abraham Palmer, which allows us to use genetic correlations to
compare IntA vs LgA, addressing a unique question: to what extent are the genes that influence the
development of addiction-like behavior with LgA similar/different than with IntA? Finally, we will use RNA
sequencing to compare how transcriptomic profiles are altered by drug exposure during IntA and LgA, enabling
us to determine which gene networks are associated with (1) escalation of intake during LgA vs IntA, (2)
incentive sensitization during IntA, and (3) compulsive drug intake during IntA and LgA.

## Key facts

- **NIH application ID:** 9971503
- **Project number:** 5P50DA037844-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Paul J Meyer
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $330,289
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971503

## Citation

> US National Institutes of Health, RePORTER application 9971503, Center for Genetic Studies of Drug Abuse in Outbred Rats (5P50DA037844-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9971503. Licensed CC0.

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