Involvement of local serotonin-2A but not serotonin-1B receptors in the reinforcing effects of ethanol within the posterior ventral tegmental area of female Wistar rats

Zheng Ming Ding, Jamie E. Toalston, Scott M. Oster, William J. McBride, Zachary Rodd

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Rationale: Previous studies indicated that ethanol could be self-infused into the posterior ventral tegmental area (p-VTA) and that activation of local serotonin-3 (5-HT3) receptors was involved. 5-HT1B and 5-HT2A receptors are involved in the effects of 5-HT and ethanol on VTA dopamine neurons. Objective: The current study used the intracranial self-administration (ICSA) procedure to determine the involvement of local 5-HT1B and 5-HT2A receptors in the self-infusion of ethanol into the p-VTA. Materials and methods: Female Wistar rats were implanted unilaterally with a guide cannula aimed at the p-VTA. Seven days after surgery, rats were placed into the two-lever operant conditioning chambers for ICSA tests. The tests consisted of four acquisition sessions with self-infusion of 200 mg% ethanol alone, two or three sessions with co-infusion of the 5-HT 1B antagonist GR 55562 (10, 100, or 200 μM) or the 5-HT 2A antagonist R-96544 (10, 100, or 200 μM) with 200 mg% ethanol, and one final session with 200 mg% ethanol alone. Results: During the acquisition sessions, all rats readily self-infused ethanol and discriminated the active from inactive lever. Co-infusion of GR 55562, at all three doses, had no effect on the self-infusion of ethanol. In contrast, co-infusion of R-96544, at the two higher doses, attenuated responding on the active lever for ethanol infusion (p∈<∈0.05). Conclusion: The results suggest that the reinforcing effects of ethanol within the p-VTA are modulated, at least in part, by activation of local 5-HT2A, but not 5-HT1B, receptors.

Original languageEnglish
Pages (from-to)381-390
Number of pages10
JournalPsychopharmacology
Volume204
Issue number3
DOIs
StatePublished - Jun 2009

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Receptor, Serotonin, 5-HT1B
Ventral Tegmental Area
Wistar Rats
Serotonin
Ethanol
(2R,4R)-4-hydroxy-2-(2-(2-(2-(3-methoxy)phenyl)ethyl)phenoxy)ethyl-1-methylpyrrolidine hydrochloride
Receptor, Serotonin, 5-HT2A
Serotonin Antagonists
Self Administration
Operant Conditioning
Receptors, Serotonin, 5-HT3
Dopaminergic Neurons
Ambulatory Surgical Procedures

Keywords

  • Ethanol
  • GR 55562
  • Intracranial self-administration
  • R-96544
  • Serotonin-1B receptor
  • Serotonin-2A receptor
  • Ventral tegmental area

ASJC Scopus subject areas

  • Pharmacology

Cite this

Involvement of local serotonin-2A but not serotonin-1B receptors in the reinforcing effects of ethanol within the posterior ventral tegmental area of female Wistar rats. / Ding, Zheng Ming; Toalston, Jamie E.; Oster, Scott M.; McBride, William J.; Rodd, Zachary.

In: Psychopharmacology, Vol. 204, No. 3, 06.2009, p. 381-390.

Research output: Contribution to journalArticle

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abstract = "Rationale: Previous studies indicated that ethanol could be self-infused into the posterior ventral tegmental area (p-VTA) and that activation of local serotonin-3 (5-HT3) receptors was involved. 5-HT1B and 5-HT2A receptors are involved in the effects of 5-HT and ethanol on VTA dopamine neurons. Objective: The current study used the intracranial self-administration (ICSA) procedure to determine the involvement of local 5-HT1B and 5-HT2A receptors in the self-infusion of ethanol into the p-VTA. Materials and methods: Female Wistar rats were implanted unilaterally with a guide cannula aimed at the p-VTA. Seven days after surgery, rats were placed into the two-lever operant conditioning chambers for ICSA tests. The tests consisted of four acquisition sessions with self-infusion of 200 mg{\%} ethanol alone, two or three sessions with co-infusion of the 5-HT 1B antagonist GR 55562 (10, 100, or 200 μM) or the 5-HT 2A antagonist R-96544 (10, 100, or 200 μM) with 200 mg{\%} ethanol, and one final session with 200 mg{\%} ethanol alone. Results: During the acquisition sessions, all rats readily self-infused ethanol and discriminated the active from inactive lever. Co-infusion of GR 55562, at all three doses, had no effect on the self-infusion of ethanol. In contrast, co-infusion of R-96544, at the two higher doses, attenuated responding on the active lever for ethanol infusion (p∈<∈0.05). Conclusion: The results suggest that the reinforcing effects of ethanol within the p-VTA are modulated, at least in part, by activation of local 5-HT2A, but not 5-HT1B, receptors.",
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T1 - Involvement of local serotonin-2A but not serotonin-1B receptors in the reinforcing effects of ethanol within the posterior ventral tegmental area of female Wistar rats

AU - Ding, Zheng Ming

AU - Toalston, Jamie E.

AU - Oster, Scott M.

AU - McBride, William J.

AU - Rodd, Zachary

PY - 2009/6

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N2 - Rationale: Previous studies indicated that ethanol could be self-infused into the posterior ventral tegmental area (p-VTA) and that activation of local serotonin-3 (5-HT3) receptors was involved. 5-HT1B and 5-HT2A receptors are involved in the effects of 5-HT and ethanol on VTA dopamine neurons. Objective: The current study used the intracranial self-administration (ICSA) procedure to determine the involvement of local 5-HT1B and 5-HT2A receptors in the self-infusion of ethanol into the p-VTA. Materials and methods: Female Wistar rats were implanted unilaterally with a guide cannula aimed at the p-VTA. Seven days after surgery, rats were placed into the two-lever operant conditioning chambers for ICSA tests. The tests consisted of four acquisition sessions with self-infusion of 200 mg% ethanol alone, two or three sessions with co-infusion of the 5-HT 1B antagonist GR 55562 (10, 100, or 200 μM) or the 5-HT 2A antagonist R-96544 (10, 100, or 200 μM) with 200 mg% ethanol, and one final session with 200 mg% ethanol alone. Results: During the acquisition sessions, all rats readily self-infused ethanol and discriminated the active from inactive lever. Co-infusion of GR 55562, at all three doses, had no effect on the self-infusion of ethanol. In contrast, co-infusion of R-96544, at the two higher doses, attenuated responding on the active lever for ethanol infusion (p∈<∈0.05). Conclusion: The results suggest that the reinforcing effects of ethanol within the p-VTA are modulated, at least in part, by activation of local 5-HT2A, but not 5-HT1B, receptors.

AB - Rationale: Previous studies indicated that ethanol could be self-infused into the posterior ventral tegmental area (p-VTA) and that activation of local serotonin-3 (5-HT3) receptors was involved. 5-HT1B and 5-HT2A receptors are involved in the effects of 5-HT and ethanol on VTA dopamine neurons. Objective: The current study used the intracranial self-administration (ICSA) procedure to determine the involvement of local 5-HT1B and 5-HT2A receptors in the self-infusion of ethanol into the p-VTA. Materials and methods: Female Wistar rats were implanted unilaterally with a guide cannula aimed at the p-VTA. Seven days after surgery, rats were placed into the two-lever operant conditioning chambers for ICSA tests. The tests consisted of four acquisition sessions with self-infusion of 200 mg% ethanol alone, two or three sessions with co-infusion of the 5-HT 1B antagonist GR 55562 (10, 100, or 200 μM) or the 5-HT 2A antagonist R-96544 (10, 100, or 200 μM) with 200 mg% ethanol, and one final session with 200 mg% ethanol alone. Results: During the acquisition sessions, all rats readily self-infused ethanol and discriminated the active from inactive lever. Co-infusion of GR 55562, at all three doses, had no effect on the self-infusion of ethanol. In contrast, co-infusion of R-96544, at the two higher doses, attenuated responding on the active lever for ethanol infusion (p∈<∈0.05). Conclusion: The results suggest that the reinforcing effects of ethanol within the p-VTA are modulated, at least in part, by activation of local 5-HT2A, but not 5-HT1B, receptors.

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