Strain-dependent neurochemical and neuroendocrine effects of desipramine, but not fluoxetine or imipramine, in spontaneously hypertensive and Wistar-Kyoto rats.

Spontaneously Hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats differ in their emotional responses to stress and antidepressant administration. We have analysed different neurochemical and psychoneuroendocrine responses to repeated pretreatments with fluoxetine, imipramine or desipramine (10 mg/kg p.o. daily for 4 weeks) in SHRs and WKY rats exposed to a daily 2-h restraint episode for the last 5 days of antidepressant administration. Following a 24-h wash-out period, WKY rats displayed higher plasma antidepressant and antidepressant metabolite levels than SHRs. Fluoxetine pretreatment decreased [(3)H]citalopram binding at midbrain serotonin (5-HT) transporters, whereas tricyclic and/or fluoxetine decreased [(3)H]ketanserin binding at cortical 5-HT(2A) receptors, [(3)H]CGP-12177 binding at cortical ss-adrenoceptors, and [(3)H]nisoxetine binding at midbrain noradrenaline (NA) transporters in both strains. None of the antidepressants affected [(3)H]8-hydroxy-2-(di-N-propylamino)tetralin binding at hippocampal 5-HT(1A) receptors. In WKY rats, repeated restraint triggered a desipramine-sensitive 140% increase in hypothalamus [(3)H]nisoxetine binding; moreover, plasma adrenocorticotropin-releasing hormone responses to a 5-min open field test were amplified by prior repeated restraint in both strains, but desipramine prevented such an amplification in WKY rats only. However, neither elevated plus-maze nor open field behaviors of SHRs and WKY rats were affected by desipramine pretreatment. Thus, the SHR and WKY rat strains may prove useful in understanding how genetic differences in noradrenergic responses to repeated stress and desipramine treatment impact on adaptive processes.

Post-ECT agitation and plasma lactate concentrations.

This prospective study evaluated the hypothesis that emergence agitation after electroconvulsive therapy (ECT) could be caused by lactate-induced panic secondary to insufficient neuromuscular blockade. Plasma lactate levels were measured before and after 245 consecutive ECT sessions in 37 patients monitored for evidence of post-ECT agitation. ECT was administered using a brief-pulse, rectangular, constant-current device through bilaterally placed electrodes under general anesthesia and neuromuscular blockade. Agitation was observed in 7% of all ECT sessions. No significant difference could be found in pre-ECT lactate levels. However, mean post-ECT lactate levels in agitated sessions were significantly greater than those in nonagitated sessions (4.77 versus 2.54 mmol/l, p < 0.05). An increase (+27%) in the pre-ECT succinylcholine dose for those patients who previously had repeated post-ECT agitation resulted in cessation of post-ECT agitation and return of the formerly high post-ECT lactate levels to normal (1.61 versus 2.07 mmol/l). Although the number of patients who had post-ECT agitation was small, the data support the hypothesis that post-ECT agitation might be a manifestation of lactate-induced panic.

Effects of repeated fluoxetine on anxiety-related behaviours, central serotonergic systems, and the corticotropic axis axis in SHR and WKY rats.

In keeping with the anxiolytic property of selective serotonin reuptake inhibitors (SSRIs) in humans, we have examined in the spontaneously hypertensive rat (SHR) and the Wistar-Kyoto (WKY) rat, which display low and high anxiety, respectively, some psychoneuroendocrine effects of a repeated treatment with the SSRI fluoxetine (5 or 10 mg/kg daily, for 3 weeks). Two days after the last injection, plasma levels of fluoxetine were not detectable whereas those of its metabolite, norfluoxetine, were present to similar extents in both strains. By means of the elevated plus-maze test (29-30 h after the 13th administration of fluoxetine) and an open field test (48 h after the last injection of fluoxetine), it was observed that fluoxetine pretreatment did not yield anxiolysis; hence, some, but not all, behaviours were indicative of anxiety and hypolocomotion (as assessed through principal component analyses and acute diazepam studies). In both strains, the 10 mg/kg dose of fluoxetine decreased hypothalamus 5-HT and 5-HIAA levels, and reduced midbrain and/or hippocampus [3H]citalopram binding at 5-HT transporters, but did not affect [3H]8-hydroxy-2-(di-N-propylamino)tetralin binding at hippocampal 5-HT1A receptors. However, the fluoxetine-elicited reduction in hippocampal 5-HT transporter binding was much more important in WKY than in SHR rats, this strain-dependent effect being associated in WKY rats with a reduction in cortical [3H]ketanserin binding at 5-HT2A receptors. Lastly, in WKY rats, repeated fluoxetine administration increased adrenal weights and the plasma corticosterone response to open field exposure, but did not affect the binding capacities of hippocampal mineralocorticoid and glucocorticoid receptors. These data show that key psychoneuroendocrine responses to repeated fluoxetine administration may be strain-dependent, and that repeated fluoxetine administration does not yield anxiolysis, as assessed by two standard tests of emotivity.

[Evaluation of the use of psychotropic drugs from urine samples from subjects attending for the first time a clinic specializing in opium addiction]. / Evaluation de l'usage des psychotropes à partir d'échantillons urinaires chez des sujets s'adressant pour la première fois à une consultation spécialisée pour toxicomanie opiacée.

OBJECTIVES: Determine how well drug abusers requesting care accept urine sampling and the reliability of this method for evaluating drug use. METHODS: Subjects attending a specialized drug abuse clinic for the first time were requested to provide a urine sample for semiquantitative analysis using an immunological technique to identify the following substances: barbiturates, benzodiazepines, opiates, cocaine, amphetamines, cannabis, and dextropropoxyphen. RESULTS: All 98 subjects included in the study accepted the urine sample. More than 80% of the samples were positive for 1, 2 or 3 substances. The most frequent were, in decreasing order, opiates, cannabis, benzodiazepines and dextropropoxyphen. Among the opiate-positive subjects (70%), 80% were positive for 2 other substances, usually cannabis and benzodiazepines. Two-thirds of the cocaine-positive cases were observed among the most recently seen subjects. Among the 27 opiate-negative subjects, 16 stated they used buprenorphine. CONCLUSION: Within the setting of this study, urine sampling appeared to be well accepted by drug abusers. Urinalysis gave an objective evaluation of drug use and can be useful on an individual level providing complementary information to the overall examination. Urine sampling can also provide indicators for studying the evolution of drug use practices in different populations, both in a clinical and non-clinical setting.

Assay for quantitation of clozapine and its metabolite N-desmethylclozapine in human plasma by high-performance liquid chromatography with ultraviolet detection.

A high-performance liquid chromatographic method with UV detection has been developed for the analysis of clozapine and its active N-desmethylated metabolite (N-desmethylclozapine = DMC) in human plasma. A liquid/liquid procedure was used to extract clozapine and DMC from human plasma. The analysis was performed on a C8 Nucleosil column and the mobile phase comprised acetonitrile-water-Pic B5 diethylamine (63:37:25:0.04, v/v/v/v). The detection wavelength was 245 nm. The intra-assay and inter-assay precision was satisfactory within the concentration range 10-900 ng ml-1. The lower detection limit for clozapine and for DMC was 5 ng ml-1. The recovery and reproducibility values of this method were better or similar to those found by other authors. This method, which is simple, selective and avoids an evaporation step, can be used routinely for therapeutic drug monitoring.

High performance liquid chromatography with ultraviolet detection used for laboratory routine determination of fluvoxamine in human plasma.

Fluvoxamine is an antidepressant drug introduced into the clinic in 1986. It acts by selectively inhibiting neuronal serotonin recapture. It can be quantified by several methods, including high performance liquid chromatography. The HPLC method used so far needs special equipment and has poor sensitivity. The technique is difficult and time consuming. An easier, quicker and more sensitive HPLC assay for the routine determination of fluvoxamine in human plasma has therefore been developed. After alkalinisation and direct extraction by a mixture of n-hexane-isoamylic alcohol 985: 15 (v/v) of plasma samples, the organic phases were further extracted by HCl 0.1 N. Thirty microL of the final extract (with loxapine as internal standard) were injected directly into a C-8 column with a mobile phase consisting of 370 mL acetonitrile, 0.4 mL diethylamine, 630 mL of distilled water, 25 mL pic B5. UV detection at 254 nm was used. The whole process was completed in 40 min. The detection limit was 10 ng mL-1. No interference was found either with several benzodiazepines or with antidepressant drugs commonly associated during treatments.

[Evaluation of malarial indices in the forest region of Djoum (southern Cameroon)]. / Evaluation des indices paludométriques dans la région forestière de Djoum (Sud Cameroun).

The authors report the results of a sample survey carried out in Djoum to evaluate the main malarial indexes among 0-15 years old children. These investigations suggest that malaria is hyperendemic in this forestry area, at the end of the dry season.