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Elevated Expression of Serotonin 5-HT2A Receptors in the Rat Ventral Tegmental Area Enhances Vulnerability to the Behavioral Effects of Cocaine

Bibliographic Data

ID15518014
AuthorsDavid V Herin (The University of Texas Medical Branch at Galveston, corresponding author), Marcy J Bubar (The University of Texas Medical Branch at Galveston), Patricia K Seitz (The University of Texas Medical Branch at Galveston), Mary L Thomas (The University of Texas Medical Branch at Galveston), Gilbert R Hillman (The University of Texas Medical Branch at Galveston), Yevgeniya I Tarasenko (The University of Texas Medical Branch at Galveston), Ping Wu (0000-0002-0788-6268, The University of Texas Medical Branch at Galveston), Kathryn A Cunningham (0000-0002-4257-1739, The University of Texas Medical Branch at Galveston)
Year2013
Volume4
Pages2-2
Publication date2013-01-01
Peer ReviewedYes
Open AccessYes
TypeARTICLE
VenueFrontiers in Psychiatry (JOURNAL)
Journal identifiersISSN: 1664-0640 • E-ISSN: 1664-0640
PublisherFrontiers Media (PUBLISHER • CH)
DOI10.3389/fpsyt.2013.00002
PMID23390419
PMCIDPMC3565455
OpenAlexW2111300618
LanguageEN
Citations received1
References cited3

The dopamine mesocorticoaccumbens pathway which originates in the ventral tegmental area (VTA) and projects to the nucleus accumbens and prefrontal cortex is a circuit important in mediating the actions of psychostimulants. The function of this circuit is modulated by the actions of serotonin (5-HT) at 5-HT(2A) receptors (5-HT(2A)R) localized to the VTA. In the present study, we tested the hypothesis that virally mediated overexpression of 5-HT(2A)R in the VTA would increase cocaine-evoked locomotor activity in the absence of alterations in basal locomotor activity. A plasmid containing the gene for the 5-HT(2A)R linked to a synthetic marker peptide (Flag) was created and the construct was packaged in an adeno-associated virus vector (rAAV-5-HT(2A)R-Flag). This viral vector (2 μl; 10(9-10) transducing units/ml) was unilaterally infused into the VTA of male rats, while control animals received an intra-VTA infusion of Ringer's solution. Virus-pretreated rats exhibited normal spontaneous locomotor activity measured in a modified open-field apparatus at 7, 14, and 21 days following infusion. After an injection of cocaine (15 mg/kg, ip), both horizontal hyperactivity and rearing were significantly enhanced in virus-treated rats (p < 0.05). Immunohistochemical analysis confirmed expression of Flag and overexpression of the 5-HT(2A)R protein. These data indicate that the vulnerability of adult male rats to hyperactivity induced by cocaine is enhanced following increased levels of expression of the 5-HT(2A)R in the VTA and suggest that the 5-HT(2A)R receptor in the VTA plays a role in regulation of responsiveness to cocaine

5-HT receptor · Dopamine · Receptor · Serotonin · Ventral tegmental area · Vulnerability (computing · Computer Science · Medicine · Neuroscience · Neuroscience and Neuropharmacology Research · Neurotransmitter Receptor Influence on Behavior · Psychology · Receptor Mechanisms and Signaling · Internal Medicine

  • Neural Plasticity in the Ventral Tegmental Area, Aversive Motivation during Drug Withdrawal and Hallucinogenic Therapy

    Hector Vargas-Perez, Taryn E Grieder et al.•Journal of Psychoactive Drugs•2023

Unique citing works1
Citations per year0,33
Citation span2023 - 2023 (1)
Citation velocityhistorical
Highly citedNo
Citation typesNeutral: 1

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