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Modulation of the ethanol-like discriminative stimulus effects of diazepam and phencyclidine by L-type voltage-gated calcium-channel ligands in rats.
Psychopharmacology (Berl). 2000 Mar; 149(1):84-92.P

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 gamma-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.

Authors+Show Affiliations

Department of Psychology, Boston University, MA 02215-2407, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10789887

Citation

Green-Jordan, K, and K A. Grant. "Modulation of the Ethanol-like Discriminative Stimulus Effects of Diazepam and Phencyclidine By L-type Voltage-gated Calcium-channel Ligands in Rats." Psychopharmacology, vol. 149, no. 1, 2000, pp. 84-92.
Green-Jordan K, Grant KA. Modulation of the ethanol-like discriminative stimulus effects of diazepam and phencyclidine by L-type voltage-gated calcium-channel ligands in rats. Psychopharmacology (Berl). 2000;149(1):84-92.
Green-Jordan, K., & Grant, K. A. (2000). Modulation of the ethanol-like discriminative stimulus effects of diazepam and phencyclidine by L-type voltage-gated calcium-channel ligands in rats. Psychopharmacology, 149(1), 84-92.
Green-Jordan K, Grant KA. Modulation of the Ethanol-like Discriminative Stimulus Effects of Diazepam and Phencyclidine By L-type Voltage-gated Calcium-channel Ligands in Rats. Psychopharmacology (Berl). 2000;149(1):84-92. PubMed PMID: 10789887.
* Article titles in AMA citation format should be in sentence-case
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,K, AU - Grant,K A, PY - 2000/5/2/pubmed PY - 2000/8/1/medline PY - 2000/5/2/entrez SP - 84 EP - 92 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 149 IS - 1 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 gamma-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. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/10789887/Modulation_of_the_ethanol_like_discriminative_stimulus_effects_of_diazepam_and_phencyclidine_by_L_type_voltage_gated_calcium_channel_ligands_in_rats_ L2 - https://dx.doi.org/10.1007/s002139900344 DB - PRIME DP - Unbound Medicine ER -