Temporal processing of durations in the range of seconds or more is mediated by working-memory mechanisms whereas processing of brief durations in the range of milliseconds appears to be beyond cognitive control and modulated by dopaminergic activity in the basal ganglia. In the present study, the effects of the selective noradrenaline reuptake inhibitor reboxetine on temporal information processing were evaluated. In a double-blind crossover design, either placebo or 2 or 4 mg of reboxetine were administered to 24 healthy male volunteers. Performance on temporal discrimination of longer durations, as indicated by 75%-difference thresholds in relation to a 1,000-ms standard interval, was significantly improved by 2 mg of reboxetine as compared to placebo, whereas the improvement observed with the 4-mg dose just failed to reach statistical significance. There was, however, no effect of reboxetine on temporal discrimination of extremely brief durations, as indicated by threshold values in relation to a 50-ms standard interval. Findings provided additional evidence for the notion that temporal processing of durations in the range of seconds is based on working-memory processes including aspects of directed attention. In timing of brief durations in the range of milliseconds, however, noradrenergic activity did not seem to play a critical role.

Photorespiration is essential for the detoxification of glycolate and recycling of carbon to the Calvin Benson Bassham cycle. Enzymes participating in the pathway have been identified, and investigations now focus on the regulation of photorespiration by transporters and metabolites. However, regulation of photorespiration on the gene level has not been intensively studied. Here, we show that maximum transcript abundance of Glu:glyoxylate aminotransferase 1 (GGT1) is regulated by intron-mediated enhancement (IME) of the 59 leader intron rather than by regulatory elements in the 59 upstream region. The intron is rich in CT-stretches and contains the motif TGTGATTTG that is highly similar to the IME-related motif TTNGATYTG. The GGT1 intron also confers leaf-specific expression of foreign promoters. Quantitative PCR analysis and GUS activity measurements revealed that IME of the GGT1 59UTR intron is controlled on the transcriptional level. IME by the GGT1 59UTR intron was at least 2-fold. Chromatin immunoprecipitation experiments showed that the abundance of RNA polymerase II binding to the intron-less construct is reduced.

This paper investigates if the highly selective norepinephrine reuptake inhibitor reboxetine leads to a dose-dependent cortisol release and if this response depends on personality dimensions related to clinical depression in healthy volunteers. Twenty-four male subjects received placebo, 2 mg, or 4 mg reboxetine in a balanced, randomized cross-over study. Cortisol was measured in saliva at six different time-points according to the kinetics of the drug. Furthermore, several measurements of cardiovascular parameters, emotional states, and possible side-effects were obtained. Subjects were divided into two groups scoring above or below the median of a depressiveness questionnaire scale [n = 11, low (D-); n = 13, high (D+)]. Results clearly demonstrated, that reboxetine stimulates cortisol release. Whereas blood pressure was not affected, heart rate increased after 2 and 4 mg but not dose dependently. Subjects reported more non-specific arousal while the dimensions of tiredness-wakefulness and positive-negative emotional states were not affected by the drug. Somatic complaints were low and only non-specific complaints were statistically elevated but of negligible amount. Subjects classified as D+ can be characterized as high responders to the drug. This is especially true not only for cortisol increases but also for changes in heart rate and some ratings on physical complaints. Hot flushes, sweating and a throbbing sensation in blood vessels in the head were observed in D+ but only with the 4 mg dose. The results clearly demonstrate that reboxetine stimulates cortisol release and heart rate and that this is particularly pronounced in subjects scoring high on depression-related personality dimensions. Reboxetine, therefore, is a promising tool for investigating neuroendocrine response to noradrenergic challenge tests. The question whether increased responses in D+ are due to an up-regulation of receptor sensitivity as a consequence of low norepinephrine supply is discussed.

No abstract