# Serotonin-7 receptors and Alcohol-seeking Behaviors

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $453,096

## Abstract

ABSTRACT:
 Drug addiction can be characterized as a chronic reoccurring illness. The relapse rate of alcoholism is
particularly high (75-95%). It has been hypothesized that drug craving is a critical precipitating factor to
relapse and drug craving is influenced by the amount of time abstinent, the exposure to the drug-paired
environment, or drug-paired cues. Convergent data in rodents and humans have indicated that drug-paired
environment or drug-paired cues' ability to elicit drug-craving intensifies with the passage of time during
early abstinence, which can be referred to as ‘cue incubation of drug craving’. The serotonin (5-HT) system
is thought to play a role in the development of alcohol addiction as well as play an important role in the
control of drug-seeking and sensitivity to drug reward and drug cues. The 5-HT7 receptor has been
researched as a potential therapeutic target for various conditions such as anxiety, depression, neuropathic
pain, Alzheimer’s disease, and drug addiction. The activation of 5-HT7 receptors can regulate ‘behavior
control,’ drug-withdrawal symptoms, and cognitive behaviors. However, there is a gap in knowledge of the
involvement of the 5-HT7 receptor in mediating alcohol (EtOH)-seeking behaviors. Extensive preliminary
data conducted in our laboratory have indicated that the systemic and site-specific, specifically in the
nucleus accumbens shell (AcbSh), pharmacological manipulation of 5-HT7 receptor bidirectionally mediates
context- and cue-induced EtOH-seeking. There is a critical need for therapeutic treatments for EtOH-
seeking behaviors and we propose that the 5-HT7 receptors need to be further researched as potential
targets for treatments of alcohol ‘craving’ behaviors. Understanding 5-HT7 mechanisms contributing to the
‘incubation’ of cue-induced EtOH-seeking is very important for developing strategies to reduce or prevent
relapse. The Pavlovian Spontaneous Recovery (PSR) model of EtOH seeking, pharmacological techniques,
and viral vectors will be used to examine the temporal effects of ‘incubation’ of cue-induced EtOH-seeking
behaviors and determine 5-HT7 receptors' involvement in regulating these behaviors. Western blot
techniques will be used to examine cellular mechanisms in ‘behavioral control’ neural circuitry and the
alterations of 5-HT7 receptors expression. Microdialysis and pharmacological techniques will be used to
examine the involvement of 5-HT7 receptors' effects on DA and 5-HT release within the AcbSh associated
with temporal aspects of ‘incubation’ of cue-induced EtOH-seeking. Therefore, we propose to test the
hypothesis that 5-HT7 receptors mediate the incubation’ of cue-induced EtOH-seeking during abstinence by
regulating extracellular levels of DA and 5-HT in the AcbSh and that this response is mediated by the
regulation of 5HT7 receptor expression in the AcbSh dorsal raphe circuit.

## Key facts

- **NIH application ID:** 10907530
- **Project number:** 5R01AA029788-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Sheketha Renay Hauser
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $453,096
- **Award type:** 5
- **Project period:** 2023-08-15 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10907530

## Citation

> US National Institutes of Health, RePORTER application 10907530, Serotonin-7 receptors and Alcohol-seeking Behaviors (5R01AA029788-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10907530. Licensed CC0.

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