Journal article
Individual differences in dopamine uptake in the dorsomedial striatum prior to cocaine exposure predict motivation for cocaine in male rats
Neuropsychopharmacology (New York, N.Y.), v 46(10), pp 1757-1767
Sep 2021
PMID: 33953341
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
A major theme of addiction research has focused on the neural substrates of individual differences in the risk for addiction; however, little is known about how vulnerable populations differ from those that are relatively protected. Here, we prospectively measured dopamine (DA) neurotransmission prior to cocaine exposure to predict the onset and course of cocaine use. Using in vivo voltammetry, we first generated baseline profiles of DA release and uptake in the dorsomedial striatum (DMS) and nucleus accumbens of drug-naïve male rats prior to exposing them to cocaine using conditioned place preference (CPP) or operant self-administration. We found that the innate rate of DA uptake in the DMS strongly predicted motivation for cocaine and drug-primed reinstatement, but not CPP, responding when "price" was low, or extinction. We then assessed the impact of baseline variations in DA uptake on cocaine potency in the DMS using ex vivo voltammetry in naïve rats and in rats with DA transporter (DAT) knockdown. DA uptake in the DMS of naïve rats predicted the neurochemical response to cocaine, such that rats with innately faster rates of DA uptake demonstrated higher cocaine potency at the DAT and rats with DAT knockdown displayed reduced potency compared to controls. Together, these data demonstrate that inherent variability in DA uptake in the DMS predicts the behavioral response to cocaine, potentially by altering the apparent potency of cocaine.
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Details
- Title
- Individual differences in dopamine uptake in the dorsomedial striatum prior to cocaine exposure predict motivation for cocaine in male rats
- Creators
- Jessica K Shaw - Drexel UniversityI Pamela Alonso - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USAStacia I Lewandowski - Drexel UniversityMarion O Scott - University of PennsylvaniaBethan M O'Connor - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USAShaili Aggarwal - Drexel UniversityMariella De Biasi - University of PennsylvaniaOle V Mortensen - Drexel UniversityRodrigo A España - Drexel University
- Publication Details
- Neuropsychopharmacology (New York, N.Y.), v 46(10), pp 1757-1767
- Publisher
- Springer Nature
- Grant note
- R01 DA044205 / NIDA NIH HHS R01 DA049545 / NIDA NIH HHS R01 DA031900 / NIDA NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; Pharmacology and Physiology
- Web of Science ID
- WOS:000647526300001
- Scopus ID
- 2-s2.0-85105343810
- Other Identifier
- 991019167974304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences
- Pharmacology & Pharmacy
- Psychiatry