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Elevated Expression of Serotonin 5-HT(2A) Receptors in the Rat Ventral Tegmental Area Enhances Vulnerability to the Behavioral Effects of Cocaine.

Authors: Herin, DV  Bubar, MJ  Seitz, PK  Thomas, ML  Hillman, GR  Tarasenko, YI  Wu, P  Cunningham, KA 
Citation: Herin DV, etal., Front Psychiatry. 2013;4:2. doi: 10.3389/fpsyt.2013.00002.
Pubmed: (View Article at PubMed) PMID:23390419
DOI: Full-text: DOI:10.3389/fpsyt.2013.00002

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 mul; 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.

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CRRD Object Information
CRRD ID: 7257659
Created: 2013-08-28
Species: All species
Last Modified: 2013-08-28
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.