Effects of serotonin-3 receptor antagonists on the intracranial self-administration of ethanol within the ventral tegmental area of Wistar rats

Zachary Rodd, David L. McKinzie, Roberto I. Melendez, Nada Berry, James M. Murphy, William J. McBride

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Rationale: Previous work from our laboratory indicated that Wistar rats will self-administer ethanol (EtOH) directly into the posterior ventral tegmental area (VTA) and that 5-HT3 antagonists will inhibit EtOH-stimulated somatodendritic release of dopamine within the VTA. Objectives: The objective of this study was to use the intracranial self-administration procedure to determine the involvement of 5-HT3 receptors in mediating the reinforcing effects of EtOH within the VTA, and to increase our understanding of central nervous system mechanisms involved in the rewarding effects of EtOH. Methods: Adult female Wistar rats were stereotaxically implanted with guide cannulae aimed at the posterior VTA. After 1 week, rats were placed into standard two-lever experimental chambers for a total of seven sessions (4-h sessions separated by 48 h) and allowed to self-administer vehicle alone, a 5-HT3 antagonist alone, 200 mg% EtOH alone, or combinations of 200 mg% EtOH with different concentrations of a 5-HT3 antagonist (n=6-9 per group). Results: Throughout all seven sessions, Wistar rats self-infused more 200 mg% ETOH (25±5 infusions) than vehicle (5±4 infusions) or 5-HT3 antagonist (6±4 infusions) (P<0.05), and responded significantly more (P<0.05) on the active than inactive lever (e.g., 50±12 vs 12±8 responses in session 1). Co-administration of 50 μM or 100 μM ICS 205,930 with 200 mg% EtOH completely prevented the acquisition and maintenance of EtOH self-infusion into the posterior VTA. Similarly, co-administration of either 25-100 μM LY-278-584 or 10-100 μM zacopride with 200 mg% EtOH completely blocked EtOH-maintained intracranial self-administration behavior. Conclusions: The results of this study suggest that the reinforcing effects of EtOH within the posterior VTA of Wistar rats require activation of local 5-HT3 receptors.

Original languageEnglish
Pages (from-to)252-259
Number of pages8
JournalPsychopharmacology
Volume165
Issue number3
StatePublished - Jan 2003

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Receptors, Serotonin, 5-HT3
Serotonin Antagonists
Ventral Tegmental Area
Self Administration
Serotonin 5-HT3 Receptor Antagonists
Wistar Rats
Ethanol
tropisetron
Dopamine
Central Nervous System
Maintenance

Keywords

  • 5-HT receptors
  • Ethanol reinforcement
  • ICS 205,930
  • Intracranial self-administration
  • LY-278-584
  • Ventral tegmental area
  • Zacopride

ASJC Scopus subject areas

  • Pharmacology

Cite this

Effects of serotonin-3 receptor antagonists on the intracranial self-administration of ethanol within the ventral tegmental area of Wistar rats. / Rodd, Zachary; McKinzie, David L.; Melendez, Roberto I.; Berry, Nada; Murphy, James M.; McBride, William J.

In: Psychopharmacology, Vol. 165, No. 3, 01.2003, p. 252-259.

Research output: Contribution to journalArticle

Rodd, Zachary ; McKinzie, David L. ; Melendez, Roberto I. ; Berry, Nada ; Murphy, James M. ; McBride, William J. / Effects of serotonin-3 receptor antagonists on the intracranial self-administration of ethanol within the ventral tegmental area of Wistar rats. In: Psychopharmacology. 2003 ; Vol. 165, No. 3. pp. 252-259.
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abstract = "Rationale: Previous work from our laboratory indicated that Wistar rats will self-administer ethanol (EtOH) directly into the posterior ventral tegmental area (VTA) and that 5-HT3 antagonists will inhibit EtOH-stimulated somatodendritic release of dopamine within the VTA. Objectives: The objective of this study was to use the intracranial self-administration procedure to determine the involvement of 5-HT3 receptors in mediating the reinforcing effects of EtOH within the VTA, and to increase our understanding of central nervous system mechanisms involved in the rewarding effects of EtOH. Methods: Adult female Wistar rats were stereotaxically implanted with guide cannulae aimed at the posterior VTA. After 1 week, rats were placed into standard two-lever experimental chambers for a total of seven sessions (4-h sessions separated by 48 h) and allowed to self-administer vehicle alone, a 5-HT3 antagonist alone, 200 mg{\%} EtOH alone, or combinations of 200 mg{\%} EtOH with different concentrations of a 5-HT3 antagonist (n=6-9 per group). Results: Throughout all seven sessions, Wistar rats self-infused more 200 mg{\%} ETOH (25±5 infusions) than vehicle (5±4 infusions) or 5-HT3 antagonist (6±4 infusions) (P<0.05), and responded significantly more (P<0.05) on the active than inactive lever (e.g., 50±12 vs 12±8 responses in session 1). Co-administration of 50 μM or 100 μM ICS 205,930 with 200 mg{\%} EtOH completely prevented the acquisition and maintenance of EtOH self-infusion into the posterior VTA. Similarly, co-administration of either 25-100 μM LY-278-584 or 10-100 μM zacopride with 200 mg{\%} EtOH completely blocked EtOH-maintained intracranial self-administration behavior. Conclusions: The results of this study suggest that the reinforcing effects of EtOH within the posterior VTA of Wistar rats require activation of local 5-HT3 receptors.",
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T1 - Effects of serotonin-3 receptor antagonists on the intracranial self-administration of ethanol within the ventral tegmental area of Wistar rats

AU - Rodd, Zachary

AU - McKinzie, David L.

AU - Melendez, Roberto I.

AU - Berry, Nada

AU - Murphy, James M.

AU - McBride, William J.

PY - 2003/1

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N2 - Rationale: Previous work from our laboratory indicated that Wistar rats will self-administer ethanol (EtOH) directly into the posterior ventral tegmental area (VTA) and that 5-HT3 antagonists will inhibit EtOH-stimulated somatodendritic release of dopamine within the VTA. Objectives: The objective of this study was to use the intracranial self-administration procedure to determine the involvement of 5-HT3 receptors in mediating the reinforcing effects of EtOH within the VTA, and to increase our understanding of central nervous system mechanisms involved in the rewarding effects of EtOH. Methods: Adult female Wistar rats were stereotaxically implanted with guide cannulae aimed at the posterior VTA. After 1 week, rats were placed into standard two-lever experimental chambers for a total of seven sessions (4-h sessions separated by 48 h) and allowed to self-administer vehicle alone, a 5-HT3 antagonist alone, 200 mg% EtOH alone, or combinations of 200 mg% EtOH with different concentrations of a 5-HT3 antagonist (n=6-9 per group). Results: Throughout all seven sessions, Wistar rats self-infused more 200 mg% ETOH (25±5 infusions) than vehicle (5±4 infusions) or 5-HT3 antagonist (6±4 infusions) (P<0.05), and responded significantly more (P<0.05) on the active than inactive lever (e.g., 50±12 vs 12±8 responses in session 1). Co-administration of 50 μM or 100 μM ICS 205,930 with 200 mg% EtOH completely prevented the acquisition and maintenance of EtOH self-infusion into the posterior VTA. Similarly, co-administration of either 25-100 μM LY-278-584 or 10-100 μM zacopride with 200 mg% EtOH completely blocked EtOH-maintained intracranial self-administration behavior. Conclusions: The results of this study suggest that the reinforcing effects of EtOH within the posterior VTA of Wistar rats require activation of local 5-HT3 receptors.

AB - Rationale: Previous work from our laboratory indicated that Wistar rats will self-administer ethanol (EtOH) directly into the posterior ventral tegmental area (VTA) and that 5-HT3 antagonists will inhibit EtOH-stimulated somatodendritic release of dopamine within the VTA. Objectives: The objective of this study was to use the intracranial self-administration procedure to determine the involvement of 5-HT3 receptors in mediating the reinforcing effects of EtOH within the VTA, and to increase our understanding of central nervous system mechanisms involved in the rewarding effects of EtOH. Methods: Adult female Wistar rats were stereotaxically implanted with guide cannulae aimed at the posterior VTA. After 1 week, rats were placed into standard two-lever experimental chambers for a total of seven sessions (4-h sessions separated by 48 h) and allowed to self-administer vehicle alone, a 5-HT3 antagonist alone, 200 mg% EtOH alone, or combinations of 200 mg% EtOH with different concentrations of a 5-HT3 antagonist (n=6-9 per group). Results: Throughout all seven sessions, Wistar rats self-infused more 200 mg% ETOH (25±5 infusions) than vehicle (5±4 infusions) or 5-HT3 antagonist (6±4 infusions) (P<0.05), and responded significantly more (P<0.05) on the active than inactive lever (e.g., 50±12 vs 12±8 responses in session 1). Co-administration of 50 μM or 100 μM ICS 205,930 with 200 mg% EtOH completely prevented the acquisition and maintenance of EtOH self-infusion into the posterior VTA. Similarly, co-administration of either 25-100 μM LY-278-584 or 10-100 μM zacopride with 200 mg% EtOH completely blocked EtOH-maintained intracranial self-administration behavior. Conclusions: The results of this study suggest that the reinforcing effects of EtOH within the posterior VTA of Wistar rats require activation of local 5-HT3 receptors.

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