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

Behav Pharmacol. 2009 Feb;20(1):33-44. doi: 10.1097/FBP.0b013e3283242f2d.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • 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*


  • Carbolines
  • Receptors, GABA-A
  • Ethanol
  • Flunitrazepam
  • beta-carboline-3-carboxylic acid ethyl ester