# The role of familiarity neurocircuitry in novelty seeking

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $486,897

## Abstract

Project Summary/Abstract
Identifying factors that may predispose individuals to developing addiction is a critical component in
understanding the basis of the disease. The most common personality traits associated with addiction include
heightened novelty seeking and preference, which are associated with increased exploratory behavior in
response to novel stimuli and more interaction with novel stimuli compared to familiar stimuli when given a
choice, respectively. Genetic studies have linked novelty seeking with the dopamine (DA) neurotransmitter
system, as well as genes involved in serotonin (5-hydroxytryptophan, 5HT) signaling. However, the interaction
between 5HT and DA in brain areas and neuronal circuits involved in novelty seeking and preference are
poorly understood. Recently, we have shown that the interpeduncular nucleus (IPN) is critically involved in
novelty seeking and preference. Specifically, activation of IPN GABAergic neurons acts as a brake to reduce
exploration of novel stimuli as they become familiar. Our published and preliminary data indicate that the IPN
receives DAergic and 5HTergic inputs from the ventral tegmental area (VTA) and median raphe (MR),
respectively. We hypothesize that these two IPN afferents interact to affect novelty seeking and preference
through modulation of familiarity signaling. Aim 1 will combine optogenetics and behavior in mice to test the
hypothesis that activation of a VTA→IPN DAergic circuit prevents familiarity signaling to increase novelty
seeking and motivation to explore novel stimuli. Aim 2 will use a similar approach to determine how 5HT
receptor signaling through serotonergic input from the MR to the IPN may influence the behavioral response to
novel and familiar stimuli. Finally, Aim 3 will use a biophysical and optogenetic approach to determine how
5HT and DA interact in the IPN and how this controls novelty preference. The results from the proposed
experiments should yield significant insight into circuits critical for novelty seeking and preference and
elucidate new mechanisms underlying behavioral traits associated with addiction.

## Key facts

- **NIH application ID:** 10171833
- **Project number:** 5R01DA047678-03
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** ANDREW R TAPPER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $486,897
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10171833

## Citation

> US National Institutes of Health, RePORTER application 10171833, The role of familiarity neurocircuitry in novelty seeking (5R01DA047678-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10171833. Licensed CC0.

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