Regional heterogeneity for the intracranial self-administration of ethanol and acetaldehyde within the ventral tegmental area of alcohol-preferring (P) rats: Involvement of dopamine and serotonin

Zachary Rodd, Richard Bell, Ying Zharag, James M. Murphy, Avram Goldstein, Alejandro Zaffaroni, Ting Kai Li, William J. McBride

Research output: Contribution to journalArticle

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Abstract

The meso-limbic dopamine (DA) system has an important role in regulating alcohol drinking. Previous findings from our laboratory indicated that Wistar rats self-administered ethanol (EtOH) directly into the posterior, but not anterior, ventral tegmental area (VTA), and that coadministration of a DA D 2,3 receptor agonist or a serotonin-3 (5-HT3) receptor antagonist blocked EtOH self-administration. In addition, we reported that alcohol-preferring (P) rats self-administered acetaldehyde (ACD), the first metabolite of EtOH, into the posterior VTA. The objectives of this study were to compare the reinforcing effects of EtOH and ACD within the VTA of P rats to examine the possibility that the reinforcing effects of EtOH within the VTA may be mediated by its conversion to ACD. Adult female P rats were stereotaxically implanted with guide cannulae aimed at either the posterior or anterior VTA, At I week after surgery, rats were placed in standard two-lever (active and inactive) experimental chambers for a total of seven to eight sessions. The 4-h sessions were conducted every other day. The results indicated that (a) 75-300 mg% (17-66 mM) EtOH and 6-90 μM ACD were self-administered into the posterior, but not anterior, VTA; (b) the self-administration of 150mg% EtOH was not altered by coinfusion of a catalase inhibitor, (c) coadministration of the D2/3 agonist quinpirole (100 μM) blocked the self-infusions of 150 mg% EtOH and 23 μM ACD into the posterior VTA; and (d) coadministration of 200 μM ICS205.930 (5-HT3 receptor antagonist) prevented the self-infusion of 150 mg% EtOH, whereas concentrations of ICS 205,930 up to 400 μM had no effect on the self-infusion of 23 μM ACD into the posterior VTA. Overall, the results of this study indicate that EtOH and ACD can independently produce reinforcing effects within the posterior VTA, and that activation of DA neurons mediates these effects, Furthermore, activation of 5-HT3 receptors within the posterior VTA is involved in the self-infusion of EtOH, but not ACD.

Original languageEnglish
Pages (from-to)330-338
Number of pages9
JournalNeuropsychopharmacology
Volume30
Issue number2
DOIs
StatePublished - Feb 2005

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Ventral Tegmental Area
Self Administration
Acetaldehyde
Dopamine
Serotonin
Ethanol
Alcohols
Serotonin 5-HT3 Receptor Antagonists
Receptors, Serotonin, 5-HT3
tropisetron
Quinpirole
Limbic System
Dopaminergic Neurons
Alcohol Drinking
Catalase
Wistar Rats

Keywords

  • Acetaldehyde reinforcement
  • Dopamine D2 receptor
  • Ethanol reinforcement
  • Intracranial self-administration
  • Serotonin-3 receptor
  • Ventral tegmental area

ASJC Scopus subject areas

  • Pharmacology

Cite this

Regional heterogeneity for the intracranial self-administration of ethanol and acetaldehyde within the ventral tegmental area of alcohol-preferring (P) rats : Involvement of dopamine and serotonin. / Rodd, Zachary; Bell, Richard; Zharag, Ying; Murphy, James M.; Goldstein, Avram; Zaffaroni, Alejandro; Li, Ting Kai; McBride, William J.

In: Neuropsychopharmacology, Vol. 30, No. 2, 02.2005, p. 330-338.

Research output: Contribution to journalArticle

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abstract = "The meso-limbic dopamine (DA) system has an important role in regulating alcohol drinking. Previous findings from our laboratory indicated that Wistar rats self-administered ethanol (EtOH) directly into the posterior, but not anterior, ventral tegmental area (VTA), and that coadministration of a DA D 2,3 receptor agonist or a serotonin-3 (5-HT3) receptor antagonist blocked EtOH self-administration. In addition, we reported that alcohol-preferring (P) rats self-administered acetaldehyde (ACD), the first metabolite of EtOH, into the posterior VTA. The objectives of this study were to compare the reinforcing effects of EtOH and ACD within the VTA of P rats to examine the possibility that the reinforcing effects of EtOH within the VTA may be mediated by its conversion to ACD. Adult female P rats were stereotaxically implanted with guide cannulae aimed at either the posterior or anterior VTA, At I week after surgery, rats were placed in standard two-lever (active and inactive) experimental chambers for a total of seven to eight sessions. The 4-h sessions were conducted every other day. The results indicated that (a) 75-300 mg{\%} (17-66 mM) EtOH and 6-90 μM ACD were self-administered into the posterior, but not anterior, VTA; (b) the self-administration of 150mg{\%} EtOH was not altered by coinfusion of a catalase inhibitor, (c) coadministration of the D2/3 agonist quinpirole (100 μM) blocked the self-infusions of 150 mg{\%} EtOH and 23 μM ACD into the posterior VTA; and (d) coadministration of 200 μM ICS205.930 (5-HT3 receptor antagonist) prevented the self-infusion of 150 mg{\%} EtOH, whereas concentrations of ICS 205,930 up to 400 μM had no effect on the self-infusion of 23 μM ACD into the posterior VTA. Overall, the results of this study indicate that EtOH and ACD can independently produce reinforcing effects within the posterior VTA, and that activation of DA neurons mediates these effects, Furthermore, activation of 5-HT3 receptors within the posterior VTA is involved in the self-infusion of EtOH, but not ACD.",
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AU - Li, Ting Kai

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