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

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 α7 receptors in attentional performance of mice and in effects of nicotine. MATERIALS AND METHODS: Mice with targeted deletion of the gene coding for the α7 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 α7(−/−) (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 α7(−/−) 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 α7(−/−) and wild-type mice. CONCLUSIONS: α7 nicotinic receptor knockout mice are impaired in performance of the 5-CSRTT, suggesting a possible role for α7 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.