# Cerebellum and Addiction

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2021 · $739,434

## Abstract

Abstract
There is broad agreement that the cerebellum does more than just coordinate movement, with clear
indications that it participates in a number of cognitive functions, and that its dysfunction may
contribute to mental health disorders such as schizophrenia, autism, and addiction. Yet, compared to
studies aimed at understanding the contribution of the cerebellum to motor coordination, there is little
research focused on elucidating the non-motor functions of the cerebellum, and our understanding of
its cognitive functions is rudimentary at best.
The literature provides compelling evidence consistent with the idea that the cerebellum contributes to
addiction and drug-seeking behavior both in experimental animals and in humans. However, the nature
of this contribution has remained, by and large, unexplored. Our pilot data reveal a potential substrate
for this effect: a previously little-appreciated direct projection from the cerebellum to the ventral
tegmental area (VTA). Because the VTA is the seat of the mesolimbic dopamine projection that is
critically important in addiction and reward, we propose the overarching hypothesis that the direct
cerebellum to VTA projection (Cb→VTA) is a critical element of the neural circuitry underlying drug-
seeking and natural reward-seeking behavior, as well as drug and natural reinforcement.
A primary aim of the current proposal is to delineate, using state-of-the-art anatomical and physiological
approaches, the pathways by which the cerebellum can affect the activity of neurons in the VTA, and
also those in the prefrontal cortex and nucleus accumbens (two additional brain regions which are
target of the VTA projections and are intimately associated with addictive behavior). To complement
and expand upon the anatomical and physiological studies, an additional goal is to directly examine the
potential utility of cerebellar projections to the VTA in acquisition and expression of addictive behavior
using behavioral experiments during which the relevant cerebellar pathways are optogenetically or
chemogenetically manipulated.
Successful completion of the proposed aims would not only advance our understanding of the non-
motor functions of the cerebellum, but has the potential to substantiate a number of mechanistic
hypotheses on acquisition and extinction of addictive behaviors. Such knowledge, while fundamental
basic science in nature, in the future may contribute to new insights for treatment of drug abusers and
prevention of relapse after treatment.

## Key facts

- **NIH application ID:** 10221659
- **Project number:** 5R01DA044761-06
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Kamran Khodakhah
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $739,434
- **Award type:** 5
- **Project period:** 2017-09-30 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10221659

## Citation

> US National Institutes of Health, RePORTER application 10221659, Cerebellum and Addiction (5R01DA044761-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10221659. Licensed CC0.

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