# Mechanisms of Dopamine Action in Learning: Implications for Addiction

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $471,633

## Abstract

Project summary
Mesolimbic dopamine, along with its ventral striatal targets, plays a major role in
Pavlovian reward learning. Pavlovian reward learning processes underlie many aspects
of drug seeking behavior and play a critical role in drug relapse. Instrumental learning
processes also form a fundamental element of drug seeking behavior, and may depend
on nigrostriatal dopamine innervation of dorsal striatum. Here we seek to understand
how mesolimbic and nigrostriatal dopamine action within striatal targets mediates select
components of reward-seeking behavior, and to test whether interactions between these
systems contribute to normal and pathological reward-seeking behavior. We focus on
dopamine because both natural and drug rewards activate dopamine neurons, and, as
confirmed in our recent findings, dopamine neuron activation, when substituted for
reward, drives specific forms of associative learning implicated in addictive behavior.
Here, using the Th:Cre transgenic rat to limit channelrhodopsin expression to dopamine
neurons, we take advantage of the ability to selectively activate mesolimbic dopamine
neurons to better understand their impact on behavior, neural activity, and integration of
ventral and dorsal striatal systems. We test whether mesolimbic dopamine neuron
reward-related activation recruits more dorsal striatal circuits during specific forms of
learning. A prominent hypothesis posits that reward seeking depends over time on more
dorsal striatal circuits as behavioral control becomes habitual. Thus, we also ask
whether activating mesolimbic dopamine systems can hasten development of habitual
responding for natural or drug reward. In addition, we will determine neural signals
mediating behaviors conditioned by mesolimbic dopamine activation in order to reveal
neural changes in downstream neuronal populations that mediate the performance of
these dopamine-mediated learned behaviors. These studies will provide new information
on the separate and interactive contributions of ventral and dorsal striatal circuits to
reward seeking behavior that can be initiated by dopamine, and are relevant for our
understanding of behavioral disorders involving overeating and substance use disorders.

## Key facts

- **NIH application ID:** 9897470
- **Project number:** 5R01DA035943-07
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Patricia H. Janak
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $471,633
- **Award type:** 5
- **Project period:** 2014-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897470

## Citation

> US National Institutes of Health, RePORTER application 9897470, Mechanisms of Dopamine Action in Learning: Implications for Addiction (5R01DA035943-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9897470. Licensed CC0.

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