Intracranial self-administration of cocaine within the posterior ventral tegmental area of Wistar rats: evidence for involvement of serotonin-3 receptors and dopamine neurons

Rodd, Zachary A.; Bell, Richard L.; Kuc, Kelly A.; Zhang, Ying; Murphy, James M.; McBride, William J.

doi:10.1124/jpet.104.075952

Cited by 72Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchNeural and Behavioral Psychology Studies

Intracranial self-administration of cocaine within the posterior ventral tegmental area of Wistar rats: evidence for involvement of serotonin-3 receptors and dopamine neurons

Rodd, Zachary A., Bell, Richard L., Kuc, Kelly A., Zhang, Ying, Murphy, James M., McBride, William J.·2005·The Journal of Pharmacology and Experimental Therapeutics

DOI 10.1124/jpet.104.075952

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Abstract

The rewarding properties of cocaine have been postulated to be regulated, in part, by the mesolimbic dopamine (DA) system. The present study assessed whether adult female Wistar rats would self-administer cocaine directly into the ventral tegmental area (VTA). Following guide cannulae surgery aimed at either the posterior or anterior VTA, subjects were placed in an operant box equipped with an active lever that caused the delivery of the infusate and an inactive lever that did not. Posterior and anterior VTA subjects were randomly assigned to one of six groups that self-administered either artificial cerebrospinal fluid (aCSF) or 25 to 400 pmol cocaine/100 nl in aCSF for the first four sessions, aCSF in sessions 5 and 6, and the acquisition dose of infusate during session 7. Additionally, the effects of increasing the time-out period, higher concentrations of cocaine, coadministration of a 5HT3 antagonist, and coadministration of a D2/3 agonist on self-infusion of cocaine were determined. Self-infusions were maintained when the time-out period was extended from 5 to 25 s. Coinfusion of a 5HT3 antagonist or D2/3 agonist blocked the self-infusion of cocaine. In contrast, rats did not self-administer 25 to 400 pmol/100 nl cocaine into the anterior VTA. Additionally, rats did not self-administer either 800 or 1600 pmol/100 nl cocaine into the posterior or anterior VTA. Overall, the data indicate that the VTA is functionally heterogeneous with regard to the rewarding actions of cocaine and that the reinforcing effects of cocaine within the posterior VTA are mediated by activation 5-HT3 receptors and DA neurons.

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Rats learn to lever-press for administration of drugs such as nicotine, carbachol, opiates, cannabinoids, cocaine, ethanol and its metabolite acetaldehyde into the posterior VTA more readily than into the anterior VTA.
“Rats learn to lever-press for administration of drugs such as nicotine (Ikemoto et al., 2006), carbachol (Ikemoto and Wise, 2002), opiates (Zangen et al., 2002), cannabinoids (Zangen et al., 2006), cocaine (Rodd et al., 2005), ethanol (Rodd-Henricks et al., 2000) and its metabolite acetaldehyde (Rodd et al., 2004) into the posterior VTA more readily than into the anterior VTA.”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Rodd et al., 2005
Rats and mice learn to self-administer opiates, cannabinoids, cocaine or ethanol into the VTA.
“Similarly, rats and mice learn to self-administer opiates (Bozarth and Wise, 1981; Welzl et al., 1989; David and Cazala, 1994a; 1994b; Devine and Wise, 1994), cannabinoids (Zangen et al., 2006), cocaine (David et al., 2004; Rodd et al., 2005) or ethanol (Gatto et al., 1994; Rodd-Henricks et al., 2000) into the VTA.”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Rodd et al., 2005

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Authors: Rodd, Z. A., Bell, R. L., Kuc, K. A., Zhang, Y., Murphy, J. M., & McBride, W. J.
Affiliations: Indiana University School of Medicine (US)
Indiana University Bloomington (US)
Indiana University – Purdue University Indianapolis (US)
ORCID: Rodd, Zachary A.
Bell, Richard L.
Zhang, Ying
McBride, William J.
Venue: The Journal of Pharmacology and Experimental Therapeutics
Publisher: Elsevier BV
Published: 2005-04
Volume: 313
Issue: 1
Pages: 134-145
ISSN: 0022-3565 (ISSN-L)
DOI: 10.1124/jpet.104.075952
OpenAlex: W2112594369
Cited by: 72
References: 58
Citations by year: 2025: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 1 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 4 · 2012: 3
FWCI: 1.93
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Alcohol Abuse and Alcoholism (AA 10721, R01AA012262, AA 12262, R01AA010721)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords: cocaine self-administration, ventral tegmental area, dopaminergic neurons, cocaine reward, mesolimbic dopamine system, 5-HT3 receptor antagonists, female rats
MeSH terms: Tropisetron, Animals, Cocaine, Conditioning, Operant, Dopamine, Dose-Response Relationship, Drug, Female, Indoles, Injections, Neurons, Self Administration, Rats, Wistar, Ventral Tegmental Area, Dopamine Agonists, Quinpirole, Cocaine-Related Disorders, Receptors, Serotonin, 5-HT3, Rats

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Intracranial self-administration of cocaine within the posterior ventral tegmental area of Wistar rats: evidence for involvement of serotonin-3 receptors and dopamine neurons

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