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.

Patients with schizophrenia exhibit deficits in a range of cognitive functions, particularly working and episodic memory, which are thought to be core features of the disorder. Memory dysfunction in schizophrenia is familial and thus a promising endophenotype for genetic studies. Both human and animal studies suggest a role for the neural nicotinic acid receptor family in cognition and specifically the a7-receptor subunit in schizophrenia and its endophenotypes. Consequently, we tested mice lacking the a7 subunit of the neural nicotinic receptor (B6.129S7-Chrna7 tm1Bay /J) in the delayed matching-toplace (DMP) task of the Morris water maze, a measure of working/episodic memory akin to human episodic memory. We report that a minor impairment in a7 knockout mice was observed in the DMP task, with knockout mice taking longer to find the hidden platform than their wildtype controls. This suggests a role for the a7 subunit in working/episodic memory and a potential role for the a7 neural nicotinic receptor gene (CHRNA7) in schizophrenia and its endophenotypes.

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BackgroundOsteoporosis and an increased fracture risk are common in Duchenne muscular dystrophy (DMD). Corticosteroid therapy given to prolong mobility increases the severity of osteoporosis and risk of fracture which can have serious functional consequences.AimsTo examine biphosphonate effect on bone mineral density (BMD) in steroid treated boys with DMD and low BMD.MethodsThe authors retrospectively reviewed case notes of 22 patients with DMD for details of fractures, BMD z-scores at the lumbar spine, regimen cumulative corticosteroid use and biphosphonate treatment.Results19/22 patients were treated with corticosteroids. Mean age was 11.7 years (6.3–21.3 years) and the mean duration of steroid intake was 4.1 years (0.5–6 years). 7/19 patients taking corticosteroids had 10 incidents of bone fractures. Four incidents (40%) were vertebral fractures and the rest were long bone fractures. The mean spinal z-score of patients on steroids was −1.75 while for those without steroid treatment was −1.8 (p value: 0.9). Six patients on steroids were treated with oral risedronate 35 mg every 2 weeks of which five had good compliance. Only one incident of fracture was recorded while the patients were on risedronate (p value: 0.05). The mean spinal z-scores before and after residronate treatment was −2.04 and −1.32, respectively (p value: 0.242).ConclusionsThe boys with DMD treated with steroids are at risk of bone fractures, particularly the vertebrae. The incidence of vertebral fractures in this group is lower than that quoted by the previous authors (75%). The BMD z-score was almost same for patients with and without steroid treatment. In steroid-treated boys, biphosphonate had a positive effect on reduction in the incidence of fractures and on BMD z-score though the improvement is not statistically significant.