Modulation of the ethanol-like discriminative stimulus effects of diazepam and phencyclidine by L-type voltage-gated calcium-channel ligands in rats

Kristen Green-Jordan, Kathleen (Kathy) Grant

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Rationale: Administration of voltage-gated Calcium-channel (VGCC) modulators with ethanol can result in enhancement or attenuation of some behavioral effects of ethanol, including its discriminative stimulus effects. Objectives: The present study used a drug-discrimination paradigm to characterize modulation of the ethanol-like discriminative stimulus effects of a γ-amino-butyric acid (GABA)(A) and N-methyl-D-aspartate (NMDA) ligand by administration of VGCC ligands. Methods: Two groups of adult male Long- Evans rats were trained to discriminate either 1.0 g/kg ethanol (n=8) or 2.0 g/kg ethanol (n=9) from water under a fixed-ratio (FR) 20 schedule of food presentation. Following training, ethanol substitution tests were conducted with cumulative doses of the GABA(A)-positive modulator diazepam (0.3-10 mg/kg, i.p.) (DZP) and the uncompetitive NMDA antagonist phencyclidine (0.3- 5.6 mg/kg, i.p) (PCP). Next, a single dose of the VGCC antagonist nimodipine, nifedipine, isradipine, or the VGCC agonist (-)-BAY k 8644 (0.3 mg/kg, i.p.) was administered prior to a cumulative DZP or PCP dose-response determination. Results: None of the VGCC modulators produced robust or consistent alterations in the ethanol-like discriminative stimulus effects of DZP in animals trained with either 1.0 g/kg or 2.0 g/kg ethanol. However, the ethanol-like discriminative stimulus effects of PCP were significantly enhanced in the presence of the VGCC antagonists and attenuated in the presence of the agonist in animals trained with 2.0 g/kg ethanol. Conclusions: Overall, these data show that VGCC modulation is not a robust component of ethanol-like discriminative stimulus effects of DZP in animals trained with 1.0 g/kg or 2.0 g/kg ethanol. However, the ethanol-like effects of PCP, particularly at higher training doses, appear to be modulated by dihydropyridine-sensitive VGCCs.

Original languageEnglish (US)
Pages (from-to)84-92
Number of pages9
JournalPsychopharmacology
Volume149
Issue number1
StatePublished - 2000
Externally publishedYes

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Ligand-Gated Ion Channels
Phencyclidine
Calcium Channels
Diazepam
Ethanol
Calcium Channel Blockers
N-Methylaspartate
gamma-Aminobutyric Acid
Calcium Channel Agonists
Isradipine
Nimodipine
Long Evans Rats
Butyric Acid
Nifedipine

Keywords

  • Drug discrimination
  • Ethanol
  • GABA(A)
  • NMDA
  • Voltage-gated calcium channel

ASJC Scopus subject areas

  • Pharmacology

Cite this

@article{2187fac908a64b7d99b2da30d1d70bf0,
title = "Modulation of the ethanol-like discriminative stimulus effects of diazepam and phencyclidine by L-type voltage-gated calcium-channel ligands in rats",
abstract = "Rationale: Administration of voltage-gated Calcium-channel (VGCC) modulators with ethanol can result in enhancement or attenuation of some behavioral effects of ethanol, including its discriminative stimulus effects. Objectives: The present study used a drug-discrimination paradigm to characterize modulation of the ethanol-like discriminative stimulus effects of a γ-amino-butyric acid (GABA)(A) and N-methyl-D-aspartate (NMDA) ligand by administration of VGCC ligands. Methods: Two groups of adult male Long- Evans rats were trained to discriminate either 1.0 g/kg ethanol (n=8) or 2.0 g/kg ethanol (n=9) from water under a fixed-ratio (FR) 20 schedule of food presentation. Following training, ethanol substitution tests were conducted with cumulative doses of the GABA(A)-positive modulator diazepam (0.3-10 mg/kg, i.p.) (DZP) and the uncompetitive NMDA antagonist phencyclidine (0.3- 5.6 mg/kg, i.p) (PCP). Next, a single dose of the VGCC antagonist nimodipine, nifedipine, isradipine, or the VGCC agonist (-)-BAY k 8644 (0.3 mg/kg, i.p.) was administered prior to a cumulative DZP or PCP dose-response determination. Results: None of the VGCC modulators produced robust or consistent alterations in the ethanol-like discriminative stimulus effects of DZP in animals trained with either 1.0 g/kg or 2.0 g/kg ethanol. However, the ethanol-like discriminative stimulus effects of PCP were significantly enhanced in the presence of the VGCC antagonists and attenuated in the presence of the agonist in animals trained with 2.0 g/kg ethanol. Conclusions: Overall, these data show that VGCC modulation is not a robust component of ethanol-like discriminative stimulus effects of DZP in animals trained with 1.0 g/kg or 2.0 g/kg ethanol. However, the ethanol-like effects of PCP, particularly at higher training doses, appear to be modulated by dihydropyridine-sensitive VGCCs.",
keywords = "Drug discrimination, Ethanol, GABA(A), NMDA, Voltage-gated calcium channel",
author = "Kristen Green-Jordan and Grant, {Kathleen (Kathy)}",
year = "2000",
language = "English (US)",
volume = "149",
pages = "84--92",
journal = "Psychopharmacology",
issn = "0033-3158",
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TY - JOUR

T1 - Modulation of the ethanol-like discriminative stimulus effects of diazepam and phencyclidine by L-type voltage-gated calcium-channel ligands in rats

AU - Green-Jordan, Kristen

AU - Grant, Kathleen (Kathy)

PY - 2000

Y1 - 2000

N2 - Rationale: Administration of voltage-gated Calcium-channel (VGCC) modulators with ethanol can result in enhancement or attenuation of some behavioral effects of ethanol, including its discriminative stimulus effects. Objectives: The present study used a drug-discrimination paradigm to characterize modulation of the ethanol-like discriminative stimulus effects of a γ-amino-butyric acid (GABA)(A) and N-methyl-D-aspartate (NMDA) ligand by administration of VGCC ligands. Methods: Two groups of adult male Long- Evans rats were trained to discriminate either 1.0 g/kg ethanol (n=8) or 2.0 g/kg ethanol (n=9) from water under a fixed-ratio (FR) 20 schedule of food presentation. Following training, ethanol substitution tests were conducted with cumulative doses of the GABA(A)-positive modulator diazepam (0.3-10 mg/kg, i.p.) (DZP) and the uncompetitive NMDA antagonist phencyclidine (0.3- 5.6 mg/kg, i.p) (PCP). Next, a single dose of the VGCC antagonist nimodipine, nifedipine, isradipine, or the VGCC agonist (-)-BAY k 8644 (0.3 mg/kg, i.p.) was administered prior to a cumulative DZP or PCP dose-response determination. Results: None of the VGCC modulators produced robust or consistent alterations in the ethanol-like discriminative stimulus effects of DZP in animals trained with either 1.0 g/kg or 2.0 g/kg ethanol. However, the ethanol-like discriminative stimulus effects of PCP were significantly enhanced in the presence of the VGCC antagonists and attenuated in the presence of the agonist in animals trained with 2.0 g/kg ethanol. Conclusions: Overall, these data show that VGCC modulation is not a robust component of ethanol-like discriminative stimulus effects of DZP in animals trained with 1.0 g/kg or 2.0 g/kg ethanol. However, the ethanol-like effects of PCP, particularly at higher training doses, appear to be modulated by dihydropyridine-sensitive VGCCs.

AB - Rationale: Administration of voltage-gated Calcium-channel (VGCC) modulators with ethanol can result in enhancement or attenuation of some behavioral effects of ethanol, including its discriminative stimulus effects. Objectives: The present study used a drug-discrimination paradigm to characterize modulation of the ethanol-like discriminative stimulus effects of a γ-amino-butyric acid (GABA)(A) and N-methyl-D-aspartate (NMDA) ligand by administration of VGCC ligands. Methods: Two groups of adult male Long- Evans rats were trained to discriminate either 1.0 g/kg ethanol (n=8) or 2.0 g/kg ethanol (n=9) from water under a fixed-ratio (FR) 20 schedule of food presentation. Following training, ethanol substitution tests were conducted with cumulative doses of the GABA(A)-positive modulator diazepam (0.3-10 mg/kg, i.p.) (DZP) and the uncompetitive NMDA antagonist phencyclidine (0.3- 5.6 mg/kg, i.p) (PCP). Next, a single dose of the VGCC antagonist nimodipine, nifedipine, isradipine, or the VGCC agonist (-)-BAY k 8644 (0.3 mg/kg, i.p.) was administered prior to a cumulative DZP or PCP dose-response determination. Results: None of the VGCC modulators produced robust or consistent alterations in the ethanol-like discriminative stimulus effects of DZP in animals trained with either 1.0 g/kg or 2.0 g/kg ethanol. However, the ethanol-like discriminative stimulus effects of PCP were significantly enhanced in the presence of the VGCC antagonists and attenuated in the presence of the agonist in animals trained with 2.0 g/kg ethanol. Conclusions: Overall, these data show that VGCC modulation is not a robust component of ethanol-like discriminative stimulus effects of DZP in animals trained with 1.0 g/kg or 2.0 g/kg ethanol. However, the ethanol-like effects of PCP, particularly at higher training doses, appear to be modulated by dihydropyridine-sensitive VGCCs.

KW - Drug discrimination

KW - Ethanol

KW - GABA(A)

KW - NMDA

KW - Voltage-gated calcium channel

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