Impaired performance of alpha7 nicotinic receptor knockout mice in the five-choice serial reaction time task

Psychopharmacology (Berl). 2006 Dec;189(2):211-23. doi: 10.1007/s00213-006-0549-2. Epub 2006 Sep 20.


Rationale: Nicotinic receptors have been implicated in attentional performance. Nicotine can improve attention in animals and humans, but knowledge about relevant receptor subtypes is very limited.

Objectives: The aim was to examine the role of alpha7 receptors in attentional performance of mice and in effects of nicotine.

Materials and methods: Mice with targeted deletion of the gene coding for the alpha7 subunit of nicotinic receptors and wild-type controls were trained on a five-choice serial reaction time task with food reinforcers presented under varying parametric conditions. Nicotine was administered in a range of doses (0.001-1.0 mg/kg sc), including those reported to enhance attentional performance.

Results: Initially the alpha7(-/-) (knockout) mice responded less accurately and made more anticipatory responses. After task parameters were altered so that the time allowed for responding was reduced and anticipatory (impulsive) responses were punished by a time-out, the pattern of performance deficits changed; there were increased omission errors in alpha7(-/-) mice but normal levels of accuracy and anticipatory responding. Nicotine did not improve any measure of performance, either with the original training parameters or after retraining; the largest dose used (1.0 mg/kg) produced a general impairment of responding in alpha7(-/-) and wild-type mice.

Conclusions: alpha7 nicotinic receptor knockout mice are impaired in performance of the 5-CSRTT, suggesting a possible role for alpha7 receptors in attentional processing. However, identification of a protocol for assessing attention-enhancing effects of nicotine in mice may require further modifications of test procedures or the use of different strains of animal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Attention / drug effects
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology*
  • Dose-Response Relationship, Drug
  • Ganglionic Stimulants / administration & dosage
  • Ganglionic Stimulants / pharmacology
  • Genotype
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nicotine / administration & dosage
  • Nicotine / pharmacology
  • Psychomotor Performance / drug effects
  • Psychomotor Performance / physiology*
  • Reaction Time / drug effects
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / physiology*
  • Reinforcement, Psychology
  • Serial Learning / drug effects
  • alpha7 Nicotinic Acetylcholine Receptor


  • Chrna7 protein, human
  • Chrna7 protein, mouse
  • Ganglionic Stimulants
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • Nicotine