Antidepressant drugs specifically inhibiting noradrenaline reuptake enhance recognition memory in rats

Behav Neurosci. 2015 Dec;129(6):701-8. doi: 10.1037/bne0000100. Epub 2015 Oct 26.

Abstract

Patients suffering from major depression often experience memory deficits even after the remission of mood symptoms, and many antidepressant drugs do not affect, or impair, memory in animals and humans. However, some antidepressant drugs, after a single dose, enhance cognition in humans (Harmer et al., 2009). To compare different classes of antidepressant drugs for their potential as memory enhancers, we used a version of the novel object recognition task in which rats spontaneously forget objects 24 hr after their presentation. Antidepressant drugs were injected systemically 30 min before or directly after the training phase (Session 1 [S1]). Post-S1 injections were used to test for specific memory-consolidation effects. The noradrenaline reuptake inhibitors reboxetine and atomoxetine, as well as the serotonin noradrenaline reuptake inhibitor duloxetine, injected prior to S1 significantly enhanced recognition memory. In contrast, the serotonin reuptake inhibitors citalopram and paroxetine and the cyclic antidepressant drugs desipramine and mianserin did not enhance recognition memory. Post-S1 injection of either reboxetine or citalopram significantly enhanced recognition memory, indicating an effect on memory consolidation. The fact that citalopram had an effect only when injected after S1 suggests that it may counteract its own consolidation-enhancing effect by interfering with memory acquisition. However, pretreatment with citalopram did not attenuate reboxetine's memory-enhancing effect. The D1/5-receptor antagonist SCH23390 blunted reboxetine's memory-enhancing effect, indicating a role of dopaminergic transmission in reboxetine-induced recognition memory enhancement. Our results suggest that antidepressant drugs specifically inhibiting noradrenaline reuptake enhance cognition and may be beneficial in the treatment of cognitive symptoms of depression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology*
  • Animals
  • Antidepressive Agents / pharmacology
  • Association Learning / drug effects
  • Association Learning / physiology
  • Excitatory Amino Acid Agonists / toxicity
  • Food
  • Ibotenic Acid / toxicity
  • Male
  • Mammillary Bodies / drug effects
  • Mammillary Bodies / physiopathology
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Neuropsychological Tests
  • Nootropic Agents / pharmacology*
  • Rats
  • Recognition, Psychology / drug effects*
  • Recognition, Psychology / physiology
  • Reversal Learning / drug effects
  • Reversal Learning / physiology
  • Spatial Memory / drug effects*
  • Spatial Memory / physiology
  • Spatial Navigation / drug effects
  • Spatial Navigation / physiology

Substances

  • Adrenergic Uptake Inhibitors
  • Antidepressive Agents
  • Excitatory Amino Acid Agonists
  • Nootropic Agents
  • Ibotenic Acid