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Discriminative stimulus effects of ethanol in rats using a three-choice ethanol-midazolam-water discrimination.
Behav Pharmacol. 2004 Dec; 15(8):555-67.BP

Abstract

Three-choice discrimination procedures are used to characterize how similar the discriminative stimulus effects of two drugs are in relation to each other. This procedure has suggested similarities between ethanol and ligands that positively modulate the gamma-aminobutyric acid type A (GABAA) receptor complex. As an extension to these studies, male Long-Evans rats were trained to discriminate midazolam (3.0 mg/kg, i.p.) from ethanol (1.0 g/kg, i.g.) from water (2.3 ml, i.g.) in a three-lever, food reinforced task. Substitution tests were conducted following administration of GABAA-positive modulators, noncompetitive N-methyl-D-aspartate (NMDA) antagonists, 5-HT1B agonists and isopropanol. Among the GABAA-positive modulators, diazepam was the only drug that completely substituted for midazolam; both pentobarbital and the neurosteroid allopregnanolone showed partial midazolam substitution. The NMDA antagonist dizocilpine substituted for ethanol, while phencyclidine showed no substitution for either ethanol or midazolam. The serotonin agonists tested also showed no substitution for either ethanol or midazolam. Isopropanol was the only other drug that completely substituted for ethanol. These data extend previous findings from an ethanol-pentobarbital-water discrimination and further define training conditions that result in a conditional basis for the ethanol discrimination where only those drugs with pharmacological heterogeneous effects similar to ethanol produce a full ethanol-like effect.

Authors+Show Affiliations

Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, NC 27157-1083, USA.No affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15577454

Citation

Porcu, P, and K A. Grant. "Discriminative Stimulus Effects of Ethanol in Rats Using a Three-choice Ethanol-midazolam-water Discrimination." Behavioural Pharmacology, vol. 15, no. 8, 2004, pp. 555-67.
Porcu P, Grant KA. Discriminative stimulus effects of ethanol in rats using a three-choice ethanol-midazolam-water discrimination. Behav Pharmacol. 2004;15(8):555-67.
Porcu, P., & Grant, K. A. (2004). Discriminative stimulus effects of ethanol in rats using a three-choice ethanol-midazolam-water discrimination. Behavioural Pharmacology, 15(8), 555-67.
Porcu P, Grant KA. Discriminative Stimulus Effects of Ethanol in Rats Using a Three-choice Ethanol-midazolam-water Discrimination. Behav Pharmacol. 2004;15(8):555-67. PubMed PMID: 15577454.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discriminative stimulus effects of ethanol in rats using a three-choice ethanol-midazolam-water discrimination. AU - Porcu,P, AU - Grant,K A, PY - 2004/12/4/pubmed PY - 2005/4/7/medline PY - 2004/12/4/entrez SP - 555 EP - 67 JF - Behavioural pharmacology JO - Behav Pharmacol VL - 15 IS - 8 N2 - Three-choice discrimination procedures are used to characterize how similar the discriminative stimulus effects of two drugs are in relation to each other. This procedure has suggested similarities between ethanol and ligands that positively modulate the gamma-aminobutyric acid type A (GABAA) receptor complex. As an extension to these studies, male Long-Evans rats were trained to discriminate midazolam (3.0 mg/kg, i.p.) from ethanol (1.0 g/kg, i.g.) from water (2.3 ml, i.g.) in a three-lever, food reinforced task. Substitution tests were conducted following administration of GABAA-positive modulators, noncompetitive N-methyl-D-aspartate (NMDA) antagonists, 5-HT1B agonists and isopropanol. Among the GABAA-positive modulators, diazepam was the only drug that completely substituted for midazolam; both pentobarbital and the neurosteroid allopregnanolone showed partial midazolam substitution. The NMDA antagonist dizocilpine substituted for ethanol, while phencyclidine showed no substitution for either ethanol or midazolam. The serotonin agonists tested also showed no substitution for either ethanol or midazolam. Isopropanol was the only other drug that completely substituted for ethanol. These data extend previous findings from an ethanol-pentobarbital-water discrimination and further define training conditions that result in a conditional basis for the ethanol discrimination where only those drugs with pharmacological heterogeneous effects similar to ethanol produce a full ethanol-like effect. SN - 0955-8810 UR - https://www.unboundmedicine.com/medline/citation/15577454/Discriminative_stimulus_effects_of_ethanol_in_rats_using_a_three_choice_ethanol_midazolam_water_discrimination_ L2 - http://dx.doi.org/10.1097/00008877-200412000-00004 DB - PRIME DP - Unbound Medicine ER -