Atomoxetine reduces hyperactive/impulsive behaviours in neurokinin-1 receptor ‘knockout’ mice

Abstract

Background

Mice with functional ablation of the neurokinin-1 receptor gene (NK1R ^−/−) display behavioural abnormalities which resemble the hyperactivity, inattention and impulsivity seen in Attention Deficit Hyperactivity Disorder (ADHD). Here, we investigated whether the established ADHD treatment, atomoxetine, alleviates these abnormalities when tested in the light/dark exploration box (LDEB) and 5-Choice Serial Reaction-Time Task (5-CSRTT).

Methods

Separate cohorts of mice were tested in the 5-CSRTT and LDEB after treatment with no injection, vehicle or atomoxetine (5-CSRTT: 0.3, 3 or 10 mg/kg; LDEB: 1, 3 or 10 mg/kg).

Results

Atomoxetine reduced the hyperactivity displayed by NK1R ^−/− mice in the LDEB at a dose (3 mg/kg) which did not affect the locomotor activity of wildtypes. Atomoxetine (10 mg/kg) also reduced impulsivity in NK1R ^−/− mice, but not wildtypes, in the 5-CSRTT. No dose of drug affected attention in either genotype.

Conclusions

This evidence that atomoxetine reduces hyperactive/impulsive behaviours in NK1R ^−/− mice consolidates the validity of using NK1R ^−/− mice in research of the aetiology and treatment of ADHD.

Highlights

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  We compared the behavioural response to atomoxetine in NK1R ^−/− and wildtype mice.

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  Atomoxetine reduced hyperactivity and impulsivity in NK1R ^−/− mice but not wildtypes.

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  This was not explained by changes in animals' emotional status or motor motivation.

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  NK1R ^−/− mice are more sensitive to atomoxetine (an ADHD treatment) than wildtypes.

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  These findings consolidate the NK1R ^−/− mouse model of ADHD.