RGD Reference Report - Effects of the 5-HT2C receptor agonist Ro60-0175 and the 5-HT2A receptor antagonist M100907 on nicotine self-administration and reinstatement. - Rat Genome Database

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Effects of the 5-HT2C receptor agonist Ro60-0175 and the 5-HT2A receptor antagonist M100907 on nicotine self-administration and reinstatement.

Authors: Fletcher, Paul J  Rizos, Zoë  Noble, Kevin  Soko, Ashlie D  Silenieks, Leo B  Lê, Anh Dzung  Higgins, Guy A 
Citation: Fletcher PJ, etal., Neuropharmacology. 2012 Jun;62(7):2288-98. doi: 10.1016/j.neuropharm.2012.01.023. Epub 2012 Feb 8.
RGD ID: 401901205
Pubmed: PMID:22342986   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neuropharm.2012.01.023   (Journal Full-text)

The reinforcing effects of nicotine are mediated in part by brain dopamine systems. Serotonin, acting via 5-HT(2A) and 5-HT(2C) receptors, modulates dopamine function. In these experiments we examined the effects of the 5-HT(2C) receptor agonist Ro60-0175 and the 5-HT(2A) receptor antagonist (M100907, volinanserin) on nicotine self-administration and reinstatement of nicotine-seeking. Male Long-Evans rats self-administered nicotine (0.03 mg/kg/infusion, IV) on either a FR5 or a progressive ratio schedule of reinforcement. Ro60-0175 reduced responding for nicotine on both schedules. While Ro60-0175 also reduced responding for food reinforcement, response rates under drug treatment were several-fold higher than in animals responding for nicotine. M100907 did not alter responding for nicotine, or food, on either schedule. In tests of reinstatement of nicotine-seeking, rats were first trained to lever press for IV infusions of nicotine; each infusion was also accompanied by a compound cue consisting of a light and tone. This response was then extinguished over multiple sessions. Injecting rats with a nicotine prime (0.15 mg/kg) reinstated responding; reinstatement was also observed when responses were accompanied by the nicotine associated cue. Ro60-0175 attenuated reinstatement of responding induced by nicotine and by the cue. The effects of Ro60-0175 on both forms of reinstatement were blocked by the 5-HT(2C) receptor antagonist SB242084. M100907 also reduced reinstatement induced by either the nicotine prime or by the nicotine associated cue. The results indicate that 5-HT(2C) and 5-HT(2A) receptors may be potential targets for therapies to treat some aspects of nicotine dependence.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HTR2AHumannicotine dependence treatmentISOHtr2a (Rattus norvegicus) RGD 
HTR2CHumannicotine dependence treatmentISOHtr2c (Rattus norvegicus) RGD 
Htr2aRatnicotine dependence treatmentIMP  RGD 
Htr2aMousenicotine dependence treatmentISOHtr2a (Rattus norvegicus) RGD 
Htr2cRatnicotine dependence treatmentIDA  RGD 
Htr2cMousenicotine dependence treatmentISOHtr2c (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Htr2a  (5-hydroxytryptamine receptor 2A)
Htr2c  (5-hydroxytryptamine receptor 2C)

Genes (Mus musculus)
Htr2a  (5-hydroxytryptamine (serotonin) receptor 2A)
Htr2c  (5-hydroxytryptamine (serotonin) receptor 2C)

Genes (Homo sapiens)
HTR2A  (5-hydroxytryptamine receptor 2A)
HTR2C  (5-hydroxytryptamine receptor 2C)


Additional Information