Research article summary (published 30 Jan 2009):

Relative potency and effectiveness of flunitrazepam, ethanol, and beta-CCE for disrupting the acquisition and retention of response sequences in rats.

Full Abstract

Despite the knowledge that gamma-aminobutyric acid(A) modulators can affect learning and memory, their capacity for disrupting each of these complex processes is rarely compared, and often mistakenly assumed to occur with identical potency. For these reasons, the effects of flunitrazepam (0.056-3.2 mg/kg), ethanol (0.25-1.5 g/kg), and ethyl-beta-carboline-3-carboxylate (beta-CCE; 1-17.8 mg/kg) were compared in groups of rats responding under baselines that assessed learning and memory separately. The first baseline was a multiple schedule of repeated acquisition and performance of tandem response sequences, whereas the second baseline was a retention or memory procedure where a tandem response sequence was acquired and then retested after a 30-min delay. Under both procedures, responding was maintained under a second-order fixed-ratio-2 schedule of food reinforcement, and incorrect responding (errors) produced a 5-s timeout. With regard to the effects of the three drugs on sequence acquisition (learning), all three drugs dose dependently decreased the overall response rate and increased the percentage of errors. Both flunitrazepam and beta-CCE affected accuracy more potently than response rate, whereas ethanol was equipotent in affecting these two dependent measures. With regard to the effects of these drugs on sequence retention (memory), both flunitrazepam and ethanol dose dependently decreased retention at doses that had little or no effect on sequence acquisition under the multiple schedule, whereas beta-CCE decreased retention and sequence acquisition similarly at the doses tested. Together, these data show that drugs with differing capacities for altering the function of gamma-aminobutyric acid(A) receptors differ in their capacity for disrupting the acquisition and retention of response sequences and that positive modulation of this receptor complex may be more predictive of disruptions in memory than disruptions in learning.

Author information

Author/s: Leonard, Stuart T (ST); Gerak, Lisa R (LR); Delatte, Marcus S (MS); Moerschbaecher, Joseph M (JM); Winsauer, Peter J (PJ);

Affiliation: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.

Grants: AA009803 (Agency:NIAAA NIH HHS) ; DA019625 (Agency:NIDA NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural

Journal: Behavioural pharmacology (Behav Pharmacol), published in England. (Language: eng)

Reference: 2009-Feb; vol 20 (issue 1) : pp 33-44

Dates: Created 2009/01/30; Completed 2009/03/03; Revised 2009/09/28;

PMID: 19179849, status: MEDLINE (last retrieval date: 9/29/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Allosteric Regulation Animals Behavior, Animal - drug effects Carbolines - pharmacology Conditioning, Operant Dose-Response Relationship, Drug Ethanol - pharmacology Flunitrazepam - pharmacology

Learning - drug effects Male Memory - drug effects Rats Rats, Long-Evans - psychology Receptors, GABA-A - drug effects Reinforcement Schedule Retention (Psychology) - drug effects

Associated Chemicals: Carbolines (0) ; Receptors, GABA-A (0) ; Flunitrazepam (1622-62-4) ; Ethanol (64-17-5) ; beta-carboline-3-carboxylic acid ethyl ester (74214-62-3)

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