Alteration of voluntary ethanol and saccharin consumption by the neurosteroid allopregnanolone in mice

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Rationale: The neurosteroid 3α-hydroxy-5α-pregnan-20-one (allopregnanolone, ALLOP) is a positive modulator of γ-aminobutyric acid type A (GABAA) receptors. Recent findings indicate that ethanol (EtOH) and ALLOP share common mechanisms of action and that ALLOP may modulate some of EtOH's abuse-related effects. Objectives: The present studies investigated whether ALLOP pretreatment altered voluntary EtOH consumption in male and female C57BL/6J mice, and voluntary saccharin and quinine consumption in male C57BL/6J mice. Methods: Mice had access to two drinking tubes containing water versus 5% or 10% (v/v) EtOH or a tastant for 2 h each day at the beginning of the dark cycle. Following establishment of stable consumption, animals received 2 days of vehicle followed by 3 days of ALLOP injections (0, 3.2, 10, or 17 mg/kg, IP), immediately prior to EtOH or tastant access. Results: Prior to injection, the 2-h baseline dose of the 10% EtOH solution consumed was 1.31 g/kg (expt 1) or 2.46 g/kg (expt 3) for male and 2.21 g/kg (expt 2) for female mice. Baseline intake of the 5% EtOH solution was 0.60 g/kg for males and 0.75 g/kg for females (expt 5). In males, ALLOP administration significantly and dose-dependently increased consumption of both EtOH solutions during the first hour of availability without affecting water intake. In females, ALLOP did not significantly alter EtOH consumption. Lastly, ALLOP significantly increased saccharin, but not quinine, consumption in males (females were not tested). Conclusions: ALLOP may increase voluntary EtOH consumption in male mice by altering its reinforcing effects. The lack of significant effect on quinine and water consumption suggests that ALLOP does not simply increase consumption of all fluids.

Original languageEnglish (US)
Pages (from-to)438-447
Number of pages10
JournalPsychopharmacology
Volume162
Issue number4
DOIs
StatePublished - 2002

Fingerprint

Pregnanolone
Saccharin
Neurotransmitter Agents
Ethanol
Quinine
Drinking
Inbred C57BL Mouse
Aminobutyrates
Injections
GABA-A Receptors

Keywords

  • C57BL/6J mice
  • Ethanol
  • GABAA receptor
  • Neurosteroid
  • Quinine
  • Reinforcement
  • Saccharin
  • Self-administration

ASJC Scopus subject areas

  • Pharmacology

Cite this

Alteration of voluntary ethanol and saccharin consumption by the neurosteroid allopregnanolone in mice. / Sinnott, Rachna S.; Phillips, Tamara; Finn, Deborah (Deb).

In: Psychopharmacology, Vol. 162, No. 4, 2002, p. 438-447.

Research output: Contribution to journalArticle

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title = "Alteration of voluntary ethanol and saccharin consumption by the neurosteroid allopregnanolone in mice",
abstract = "Rationale: The neurosteroid 3α-hydroxy-5α-pregnan-20-one (allopregnanolone, ALLOP) is a positive modulator of γ-aminobutyric acid type A (GABAA) receptors. Recent findings indicate that ethanol (EtOH) and ALLOP share common mechanisms of action and that ALLOP may modulate some of EtOH's abuse-related effects. Objectives: The present studies investigated whether ALLOP pretreatment altered voluntary EtOH consumption in male and female C57BL/6J mice, and voluntary saccharin and quinine consumption in male C57BL/6J mice. Methods: Mice had access to two drinking tubes containing water versus 5{\%} or 10{\%} (v/v) EtOH or a tastant for 2 h each day at the beginning of the dark cycle. Following establishment of stable consumption, animals received 2 days of vehicle followed by 3 days of ALLOP injections (0, 3.2, 10, or 17 mg/kg, IP), immediately prior to EtOH or tastant access. Results: Prior to injection, the 2-h baseline dose of the 10{\%} EtOH solution consumed was 1.31 g/kg (expt 1) or 2.46 g/kg (expt 3) for male and 2.21 g/kg (expt 2) for female mice. Baseline intake of the 5{\%} EtOH solution was 0.60 g/kg for males and 0.75 g/kg for females (expt 5). In males, ALLOP administration significantly and dose-dependently increased consumption of both EtOH solutions during the first hour of availability without affecting water intake. In females, ALLOP did not significantly alter EtOH consumption. Lastly, ALLOP significantly increased saccharin, but not quinine, consumption in males (females were not tested). Conclusions: ALLOP may increase voluntary EtOH consumption in male mice by altering its reinforcing effects. The lack of significant effect on quinine and water consumption suggests that ALLOP does not simply increase consumption of all fluids.",
keywords = "C57BL/6J mice, Ethanol, GABAA receptor, Neurosteroid, Quinine, Reinforcement, Saccharin, Self-administration",
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year = "2002",
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T1 - Alteration of voluntary ethanol and saccharin consumption by the neurosteroid allopregnanolone in mice

AU - Sinnott, Rachna S.

AU - Phillips, Tamara

AU - Finn, Deborah (Deb)

PY - 2002

Y1 - 2002

N2 - Rationale: The neurosteroid 3α-hydroxy-5α-pregnan-20-one (allopregnanolone, ALLOP) is a positive modulator of γ-aminobutyric acid type A (GABAA) receptors. Recent findings indicate that ethanol (EtOH) and ALLOP share common mechanisms of action and that ALLOP may modulate some of EtOH's abuse-related effects. Objectives: The present studies investigated whether ALLOP pretreatment altered voluntary EtOH consumption in male and female C57BL/6J mice, and voluntary saccharin and quinine consumption in male C57BL/6J mice. Methods: Mice had access to two drinking tubes containing water versus 5% or 10% (v/v) EtOH or a tastant for 2 h each day at the beginning of the dark cycle. Following establishment of stable consumption, animals received 2 days of vehicle followed by 3 days of ALLOP injections (0, 3.2, 10, or 17 mg/kg, IP), immediately prior to EtOH or tastant access. Results: Prior to injection, the 2-h baseline dose of the 10% EtOH solution consumed was 1.31 g/kg (expt 1) or 2.46 g/kg (expt 3) for male and 2.21 g/kg (expt 2) for female mice. Baseline intake of the 5% EtOH solution was 0.60 g/kg for males and 0.75 g/kg for females (expt 5). In males, ALLOP administration significantly and dose-dependently increased consumption of both EtOH solutions during the first hour of availability without affecting water intake. In females, ALLOP did not significantly alter EtOH consumption. Lastly, ALLOP significantly increased saccharin, but not quinine, consumption in males (females were not tested). Conclusions: ALLOP may increase voluntary EtOH consumption in male mice by altering its reinforcing effects. The lack of significant effect on quinine and water consumption suggests that ALLOP does not simply increase consumption of all fluids.

AB - Rationale: The neurosteroid 3α-hydroxy-5α-pregnan-20-one (allopregnanolone, ALLOP) is a positive modulator of γ-aminobutyric acid type A (GABAA) receptors. Recent findings indicate that ethanol (EtOH) and ALLOP share common mechanisms of action and that ALLOP may modulate some of EtOH's abuse-related effects. Objectives: The present studies investigated whether ALLOP pretreatment altered voluntary EtOH consumption in male and female C57BL/6J mice, and voluntary saccharin and quinine consumption in male C57BL/6J mice. Methods: Mice had access to two drinking tubes containing water versus 5% or 10% (v/v) EtOH or a tastant for 2 h each day at the beginning of the dark cycle. Following establishment of stable consumption, animals received 2 days of vehicle followed by 3 days of ALLOP injections (0, 3.2, 10, or 17 mg/kg, IP), immediately prior to EtOH or tastant access. Results: Prior to injection, the 2-h baseline dose of the 10% EtOH solution consumed was 1.31 g/kg (expt 1) or 2.46 g/kg (expt 3) for male and 2.21 g/kg (expt 2) for female mice. Baseline intake of the 5% EtOH solution was 0.60 g/kg for males and 0.75 g/kg for females (expt 5). In males, ALLOP administration significantly and dose-dependently increased consumption of both EtOH solutions during the first hour of availability without affecting water intake. In females, ALLOP did not significantly alter EtOH consumption. Lastly, ALLOP significantly increased saccharin, but not quinine, consumption in males (females were not tested). Conclusions: ALLOP may increase voluntary EtOH consumption in male mice by altering its reinforcing effects. The lack of significant effect on quinine and water consumption suggests that ALLOP does not simply increase consumption of all fluids.

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KW - Quinine

KW - Reinforcement

KW - Saccharin

KW - Self-administration

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