Antidepressant activity of memory-enhancing drugs in the reduction of submissive behavior model

Eur J Pharmacol. 2002 Apr 5;440(1):27-35. doi: 10.1016/s0014-2999(02)01338-9.


The present study tests the activity of nootropic drugs in a behavioral test linked to depression. This test measures the reduction of submissive behavior in a competition test as the relative success of two food-restricted rats to gain access to a feeder. Nootropic drugs tested include piracetam (2-oxo-1-pyrrolidineacetamide), aniracetam (1-(4-methoxybenzoyl)-2-pyrrolidinone), the Ampakine, Ampalex, 1-(quinoxalin-6-ylcarbonyl)piperidine, and analogs were compared to the antidepressants, fluoxetine ((+/-)-N-methyl-gamma-(4-[trifluoromethyl]phenoxy)-benzenepropanamine) and desimpramine (5H-dibenz[b,f]azepine-5-propanamine, 10,11-dihydro-N-methyl-, monohydrochloride), while the anxiolytic diazepam (7-chloro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2(1H)-one) served as a control. Drugs were given intraperitoneally for 3 weeks. The antidepressant and nootropic drugs reduced submissive behavior over time. The effect was dose dependent as measured for fluoxetine and Ampakines. The reduction of submissive behavior by Ampakines gradually faded after cessation of treatment and had a more rapid onset of activity (during the 1st week of treatment) than fluoxetine (after 2 weeks). The results suggest that Ampakines may have antidepressant activity. The potential of depression treatment with memory-enhancing drugs is hypothesized and the link between cognition and depression is discussed.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Competitive Behavior / drug effects*
  • Desipramine / pharmacology
  • Diazepam / pharmacology
  • Dioxoles / chemistry
  • Dioxoles / pharmacology
  • Dose-Response Relationship, Drug
  • Fluoxetine / pharmacology
  • Injections, Intraperitoneal
  • Male
  • Maze Learning / drug effects
  • Models, Animal
  • Nootropic Agents / pharmacology*
  • Piperidines / chemistry
  • Piperidines / pharmacology
  • Piracetam / pharmacology
  • Pyrrolidinones / pharmacology
  • Rats
  • Rats, Sprague-Dawley


  • 1-(quinoxalin-6-ylcarbonyl)piperidine
  • Antidepressive Agents
  • Dioxoles
  • Nootropic Agents
  • Piperidines
  • Pyrrolidinones
  • Fluoxetine
  • aniracetam
  • Diazepam
  • Desipramine
  • Piracetam