Journal article
Hypocretin receptor 1 knockdown in the ventral tegmental area attenuates mesolimbic dopamine signaling and reduces motivation for cocaine
Addiction biology, v 23(5), pp 1032-1045
01 Sep 2018
PMID: 28971565
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The hypocretin receptor 1 (HCRTr1) is a critical participant in the regulation of motivated behavior. Previous observations demonstrate that acute pharmacological blockade of HCRTr1 disrupts dopamine (DA) signaling and the motivation for cocaine when delivered systemically or directly into the ventral tegmental area (VTA). To further examine the involvement of HCRTr1 in regulating reward and reinforcement processing, we employed an adeno-associated virus to express a short hairpin RNA designed to knock down HCRTr1. We injected virus into the VTA and examined the effects of HCRTr1 knockdown on cocaine self-administration and DA signaling in the nucleus accumbens (NAc) core. We determined that the viral approach was effective at reducing HCRTr1 expression without affecting the expression of hypocretin receptor 2 or DA-related mRNAs. We next examined the effects of HCRTr1 knockdown on cocaine self-administration, observing delayed acquisition under a fixed-ratio schedule and reduced motivation for cocaine under a progressive ratio schedule. These effects did not appear to be associated with alterations in sleep/wake activity. Using fast-scan cyclic voltammetry, we then examined whether HCRTr1 knockdown alters DA signaling dynamics in the NAc core. We observed reduced DA release and slower uptake rate as well as attenuated cocaine-induced DA uptake inhibition in rats with knockdown of HCRTr1. These observations indicate that HCRTr1 within the VTA influence the motivation for cocaine, likely via alterations in DA signaling in the NAc.
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Details
- Title
- Hypocretin receptor 1 knockdown in the ventral tegmental area attenuates mesolimbic dopamine signaling and reduces motivation for cocaine
- Creators
- David L. Bernstein - Drexel UniversityPreeti S. Badve - Drexel UniversityJessica R. Barson - Drexel UniversityCaroline E. Bass - University at Buffalo, State University of New YorkRodrigo A. Espana - Drexel University
- Publication Details
- Addiction biology, v 23(5), pp 1032-1045
- Publisher
- Wiley
- Number of pages
- 14
- Grant note
- F31DA041199 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission R00AA021782 / NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) F31DA041199; R01DA031900; R00AA021782 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000442203900005
- Scopus ID
- 2-s2.0-85052731572
- Other Identifier
- 991019168684904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Substance Abuse