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


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


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.
Hoyle
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E
Section of Behavioural Pharmacology, Institute of Psychiatry PO49, King's College London, De Crespigny Park, London, SE5 8AF, UK.
Genn
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RF
Fernandes
C
C
Stolerman
I P
IP
D000818:Animals; D001288:Attention / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005731:Ganglionic Stimulants / Q000008:administration & dosage / Q000494:pharmacology; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology*; D011930:Reaction Time / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D012054:Reinforcement, Psychology; D012691:Serial Learning / Q000187:drug effects; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D005731:Ganglionic Stimulants; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine