The enhancement of central serotonin system function underlies the therapeutic effects of selective serotonin reuptake inhibitors (SSRIs), which have become the most commonly used class of antidepressant agents. However, many individuals experience depressive episodes that are resistant to SSRI treatment. Homeostatic mechanisms that limit the extent to which SSRIs enhance serotonergic neurotransmission have been implicated in this phenomenon. Here, we report a novel strategy for enhancing the efficacy of SSRIs. Using in vivo microdialysis methods in rats, the nonselective 5-HT 2 receptor antagonist ketanserin was observed to produce a robust augmentation of citalopram-, fluoxetine-, and sertraline-induced elevations of hippocampal extracellular serotonin levels. Similar effects were also observed in cortex. The potentiation of SSRI-induced increases in hippocampal serotonin levels was reproduced by the 5-HT 2C receptor-selective antagonists SB 242084 and RS 102221, but not by the 5-HT 2A receptor-selective antagonist MDL 100 907. Although 5-HT 2C receptor antagonists augmented the actions of SSRIs, they had no effect on extracellular serotonin levels or tail suspension responses when administered alone. These results were in strong accord with independent findings using a line of 5-HT 2C receptor-null mutant mice. Although this mutation did not affect baseline extracellular serotonin levels or tail suspension test (TST) behavior, it enhanced fluoxetine effects on serotonin levels and immobility in the TST. These findings reveal an unanticipated pharmacological action of 5-HT 2C receptors that warrants consideration in the development of novel strategies for the treatment of depression.

The velocity of the ozonisation of benzene in chloroform is proportional to the concentration of benzene and that of ozone. The reaction constant was determined a t eight temperatures between -25 and -40" C.The reaction takes place about three times more rapidly in nitroinethane than in chloroform. Aluminium chloride and ferric chloride catalyse the reaction; the velocity increases directly with the concentration of aluminium chloride. mechanism suggested in a previous publication.T h e results of our measurements are in agreement with the reaction 4 1. Introduction.Working within the framework of the researches of Wibauf and his collaborators 1 ) on the action of ozone on aromatic compounds, we have initiated an investigation into the mechanism of this reaction.In a previous paper 2 ) we have given a short description of a number of experiments, which show that the velocity of the reaction between several aromatic compounds and ozone decreases in the same order as their reactivity in electrophilic substitution reactions. Moreover boron trifluoride and aluminium chloride have a definite accelerating effect on the ozonisation of benzene derivatives. On the basis of these experiments it was concluded that the addition of ozone to these compounds takes place according to an electrophilic mechanism. Further arguments in favour of this hypothesis have been obtained by a kinetic examination of a number of ozonisation reactions. T h e results of this investigation in so far as they relate to the ozonisation of benzene are described in this communication.

An apparatus is described for the automatic quantitative registration of reduction, desorption/adsorption, and oxidation phenomena which occur when a catalyst sample is heated or cooled under temperature programming in a flowing gas that contains either hydrogen or oxygen as the reactive component. The design considerations and the automation scheme are fully discussed. A typical example of the characterization of a catalytic reforming catalyst by means of its temperature-programmed reduction, (hydrogen) desorption, and oxidation profiles is shown. Quantitative results are repeatable to within 1% relative.

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