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

• Published in: Psychopharmacologia Vol. 189; no. 2; pp. 211 - 223
• Main Authors: HOYLE, E, GENN, R. F, FERNANDES, C, STOLERMAN, I. P
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-12-2006; Springer Nature B.V; Springer-Verlag
• Subjects: Addictive behaviors; Adult and adolescent clinical studies; alpha7 Nicotinic Acetylcholine Receptor; Animal behavior; Animal cognition; Animals; Attention - drug effects; Biological and medical sciences; Conditioning, Operant - drug effects; Conditioning, Operant - physiology; Dose-Response Relationship, Drug; Drug addiction; Ganglionic Stimulants - administration & dosage; Ganglionic Stimulants - pharmacology; Genotype; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Nicotine; Nicotine - administration & dosage; Nicotine - pharmacology; Original Investigation; Psychology. Psychoanalysis. Psychiatry; Psychomotor Performance - drug effects; Psychomotor Performance - physiology; Psychopathology. Psychiatry; Psychoses; Reaction Time - drug effects; Receptors, Nicotinic - genetics; Receptors, Nicotinic - physiology; Reinforcement, Psychology; Response time; Rodents; Schizophrenia; Serial Learning - drug effects; Drug addiction; Drug abuse; Attention; Schizophrenia; Cognition; Substance abuse; Knockout; Psychosis; Alkaloid; Cholinergic receptor; Addiction; Gene; Choice reaction time; Animal; Knockout mouse; Serial reaction time; Mice; Behavior; Mutation; Performance; Nicotinic receptor; Nicotine
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-006-0549-2

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