Serotonin-3 receptors in the posterior ventral tegmental area regulate ethanol self-administration of alcohol-preferring (P) rats

Zachary Rodd, Richard Bell, Scott M. Oster, Jamie E. Toalston, Tylene J. Pommer, William J. McBride, James M. Murphy

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Several studies indicated the involvement of serotonin-3 ([5-hydroxy tryptamine] 5-HT 3) receptors in regulating alcohol-drinking behavior. The objective of this study was to determine the involvement of 5-HT 3 receptors within the ventral tegmental area (VTA) in regulating ethanol self-administration by alcohol-preferring (P) rats. Standard two-lever operant chambers (Coulbourn Instruments, Allentown, PA) were used to examine the effects of seven consecutive bilateral microinfusions of ICS 205-930 (ICS), a 5-HT 3 receptor antagonist, directly into the posterior VTA on the acquisition and maintenance of 15% (vol/vol) ethanol self-administration. P rats readily acquired ethanol self-administration by the fourth session. The three highest doses (0.125, 0.25, and 1.25μg) of ICS prevented acquisition of ethanol self-administration. During the acquisition postinjection period, all rats treated with ICS demonstrated higher responding on the ethanol lever, with the highest dose producing the greatest effect. In contrast, during the maintenance phase, the three highest doses (0.75, 1.0, and 1.25μg) of ICS significantly increased responding on the ethanol lever; after the 7-day dosing regimen, responding on the ethanol lever returned to control levels. Microinfusion of ICS into the posterior VTA did not alter the low responding on the water lever and did not alter saccharin (0.0125% wt/v) self-administration. Microinfusion of ICS into the anterior VTA did not alter ethanol self-administration. Overall, the results of this study suggest that 5-HT 3 receptors in the posterior VTA of the P rat may be involved in regulating ethanol self-administration. In addition, chronic operant ethanol self-administration and/or repeated treatments with a 5-HT 3 receptor antagonist may alter neuronal circuitry within the posterior VTA.

Original languageEnglish
Pages (from-to)245-255
Number of pages11
JournalAlcohol
Volume44
Issue number3
DOIs
StatePublished - May 2010

Fingerprint

self-administration
Receptors, Serotonin, 5-HT3
Ventral Tegmental Area
Self Administration
Rats
Ethanol
alcohol
Alcohols
Serotonin Receptors
Serotonin
tropisetron
Maintenance
Saccharin
Drinking Behavior
chamber
Level control
Alcohol Drinking
water

Keywords

  • Alcohol-preferring rats
  • Ethanol self-administration
  • ICS 205-930
  • Serotonin-3 receptor
  • Ventral tegmental area

ASJC Scopus subject areas

  • Biochemistry
  • Medicine(all)
  • Behavioral Neuroscience
  • Neurology
  • Toxicology
  • Health(social science)

Cite this

Serotonin-3 receptors in the posterior ventral tegmental area regulate ethanol self-administration of alcohol-preferring (P) rats. / Rodd, Zachary; Bell, Richard; Oster, Scott M.; Toalston, Jamie E.; Pommer, Tylene J.; McBride, William J.; Murphy, James M.

In: Alcohol, Vol. 44, No. 3, 05.2010, p. 245-255.

Research output: Contribution to journalArticle

Rodd, Zachary ; Bell, Richard ; Oster, Scott M. ; Toalston, Jamie E. ; Pommer, Tylene J. ; McBride, William J. ; Murphy, James M. / Serotonin-3 receptors in the posterior ventral tegmental area regulate ethanol self-administration of alcohol-preferring (P) rats. In: Alcohol. 2010 ; Vol. 44, No. 3. pp. 245-255.
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AB - Several studies indicated the involvement of serotonin-3 ([5-hydroxy tryptamine] 5-HT 3) receptors in regulating alcohol-drinking behavior. The objective of this study was to determine the involvement of 5-HT 3 receptors within the ventral tegmental area (VTA) in regulating ethanol self-administration by alcohol-preferring (P) rats. Standard two-lever operant chambers (Coulbourn Instruments, Allentown, PA) were used to examine the effects of seven consecutive bilateral microinfusions of ICS 205-930 (ICS), a 5-HT 3 receptor antagonist, directly into the posterior VTA on the acquisition and maintenance of 15% (vol/vol) ethanol self-administration. P rats readily acquired ethanol self-administration by the fourth session. The three highest doses (0.125, 0.25, and 1.25μg) of ICS prevented acquisition of ethanol self-administration. During the acquisition postinjection period, all rats treated with ICS demonstrated higher responding on the ethanol lever, with the highest dose producing the greatest effect. In contrast, during the maintenance phase, the three highest doses (0.75, 1.0, and 1.25μg) of ICS significantly increased responding on the ethanol lever; after the 7-day dosing regimen, responding on the ethanol lever returned to control levels. Microinfusion of ICS into the posterior VTA did not alter the low responding on the water lever and did not alter saccharin (0.0125% wt/v) self-administration. Microinfusion of ICS into the anterior VTA did not alter ethanol self-administration. Overall, the results of this study suggest that 5-HT 3 receptors in the posterior VTA of the P rat may be involved in regulating ethanol self-administration. In addition, chronic operant ethanol self-administration and/or repeated treatments with a 5-HT 3 receptor antagonist may alter neuronal circuitry within the posterior VTA.

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