# Hypocretin receptor 1 regulation of cocaine-associated behavior involves actions on heterogenous populations in the ventral tegmental area

> **NIH NIH F31** · DREXEL UNIVERSITY · 2020 · $45,520

## Abstract

Project Summary/Abstract
The hypocretin system has been shown to impact the neural processes that support cocaine use via actions on
hypocretin receptor 1 in the ventral tegmental area. Consequently, hypocretin receptors are posited to be a
potentially valuable target for the treatment of cocaine addiction. To date, however, hypocretin-based treatment
approaches have been met with limited efficacy largely due to lack of neuron-specificity of hypocretin receptor
1 manipulations. This poses a significant hurdle for understanding the therapeutic potential of hypocretin-based
treatments since hypocretin receptor 1 are present on both dopamine and GABA neurons in the ventral
tegmental area. To circumvent this limitation, I will use combinatorial viral approaches to selectively knockdown
hypocretin receptor 1 in dopamine or GABA neurons of the ventral tegmental area, thereby allowing for
selective examination of hypocretin manipulations on cocaine abuse. I will apply techniques such as ex-vivo
fast-scan cyclic voltammetry and western blotting to query the effect of cell type-specific hypocretin receptor 1
knockdown on dopamine dynamics in the nucleus accumbens at baseline and in response to cocaine. Further,
I will investigate the influence of hypocretin receptor 1 manipulations on dopamine dynamics across key
phases of cocaine abuse using fast-scan cyclic voltammetry in self-administering rats. The proposed studies
will afford the opportunity, for the first time, to uncover cell type-specific and real-time influences of hypocretin
across acquisition, maintenance, extinction, and reinstatement of cocaine self-administration. Together, these
findings will provide a more comprehensive understanding of hypocretin modulation of dopamine
neurotransmission during cocaine self-administration and uncover potential targets for future development of
treatment strategies for cocaine use disorder.

## Key facts

- **NIH application ID:** 9970151
- **Project number:** 5F31DA049458-02
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Emily Black
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2019-06-20 → 2021-06-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970151

## Citation

> US National Institutes of Health, RePORTER application 9970151, Hypocretin receptor 1 regulation of cocaine-associated behavior involves actions on heterogenous populations in the ventral tegmental area (5F31DA049458-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9970151. Licensed CC0.

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