Complex behavioural changes after odour exposure in Drosophila larvae

A variety of odorants attract Drosophila larvae, although this behaviour can be modulated by experience. For instance, larvae pre-exposed to an attractive odorant may subsequently display less attraction towards the same compound. In previous reports, this phenomenon has been interpreted as a drop in olfactory sensitivity, caused by sensory adaptation. We tried to elucidate the basis of this behavioural modification by pre-exposing larvae to various odours. After multiple pre-exposure cycles larvae were repulsed by initially attractive odours, and pre-exposure did not change the threshold concentration driving a behavioural response. We therefore believe that sensitivity to the odorant was only slightly affected in our protocol. Our results thus do not support the previous interpretation and rather suggest that olfactory pre-exposure induces a change in the hedonic value of the odour. Although we did not succeed in elucidating the exact nature of the underlying mechanism, we can reject an association of the odour with the absence of food as an interpretation of the observed behavioural changes; this is because addition of food did not abolish the repulsion to the pre-exposed odour. In addition to ruling out previous interpretations of odour pre-exposure effects, this study stresses the complexity of Drosophila larval behaviour

Residual effects of esmirtazapine on actual driving performance: overall findings and an exploratory analysis into the role of CYP2D6 phenotype

INTRODUCTION: Esmirtazapine is evaluated as a novel drug for treatment of insomnia. PURPOSE: The present study was designed to assess residual effects of single and repeated doses of esmirtazapine 1.5 and 4.5 mg on actual driving in 32 healthy volunteers in a double-blind, placebo-controlled study. Treatment with single doses of zopiclone 7.5 mg was included as active control. METHODS: Treatments were administered in the evening. Driving performance was assessed in the morning, 11 h after drug intake, in a standardized on-the-road highway driving test. The primary study parameter was standard deviation of lateral position (SDLP), a measure of "weaving". All subjects were subjected to CYP2D6 phenotyping in order to distinguish poor metabolizers from extensive metabolizers of esmirtazapine. RESULTS: Overall, esmirtazapine 1.5 mg did not produce any clinically relevant change in SDLP after single and repeated dosing. Driving impairment, i.e., a rise in SDLP, did occur after a single-dose administration of esmirtazapine 4.5 mg but was resolved after repeated doses. Acute driving impairment was more pronounced after both doses of esmirtazapine in a select group of poor metabolizers (N = 7). A single-dose zopiclone 7.5 mg also increased SDLP as expected. CONCLUSION: It is concluded that single and repeated doses of 1.5 mg esmirtazapine are generally not associated with residual impairment. Single-dose administration of 4.5 mg esmirtazapine was associated with residual impairment that generally resolved after repeated administration. Exploratory analysis in a small group of poor CYP 2D6 metabolizers suggested that these subjects are more sensitive to the impairing effects of esmirtazapine on car driving