Effect of scopolamine on the efflux of dopamine and its metabolites after clozapine, haloperidol or thioridazine

The extracellular concentrations of dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the striatum and the nucleus accumbens were measured in awake, freely-moving rats. Clozapine (20 mg/kg, i.p.) increased extracellular DA and HVA in both regions but increased DOPAC only in the striatum. Scopolamine (1 mg/kg), although it had no effect by itself in the striatum or nucleus accumbens, inhibited the ability of clozapine to increase extracellular DA, DOPAC and HVA concentrations in the striatum. The clozapine-induced increase in DA in the frontal cortex was not blocked by scopolamine. Haloperidol (1 mg/kg, i.p.) and thioridazine (10 mg/kg, i.p.) also increased extracellular DA, DOPAC and HVA in the striatum, but scopolamine pretreatment did not inhibit these increases. The results suggest that clozapine differs from haloperidol and thioridazine in that the effect of clozapine, but not that of the two neuroleptic drugs, to increase DA release in the striatum acutely depends on muscarinic receptor stimulation. These results suggest that clozapine, despite its strong muscarinic antagonist properties, does not produce full blockade of muscarinic receptors in vivo in the striatum. The interaction of clozapine with the cholinergic system in the striatum could be relevant to its lack of ability to produce extrapyramidal symptoms or tardive dyskinesia.     

Purification and characterization of a NADP+/NADPH-specific flavoprotein that is overexpressed in FdI- strains of Azotobacter vinelandii

Earlier studies have established that mutant strains of Azotobacter vinelandii that do not synthesize ferredoxin I (AvFdI) overexpress another protein designated Protein X (Morgan, T. V., Lundell, P. J., and Burgess, B. K. (1988) J. Biol. Chem. 263, 1370-1375). This protein has now been purified using two-dimensional gel electrophoresis as an assay. The purified protein is a monomer with M(r) approximately 29,000 which degrades slowly to a specific M(r) approximately 22,000 form when stored in solution. The native protein is bright yellow and contains noncovalently attached FAD that is reduced by either dithionite or NADPH without formation of a stable semiquinone. Titration with NADP+/NADPH gives an E0' value of approximately -327 mV versus SHE. Because this E0' is so close to that of the NADP+/NADPH couple it is not clear if Protein X is an NADPH oxidase or an NADP+ reductase in vivo. Comparison of the NH2-terminal sequence and other properties of Protein X with those of other proteins, suggests that it is likely to be related to the Escherichia coli ferredoxin NADP+ reductase (the fpr gene product), and affinity chromatography shows that Protein X binds specifically to AvFdI.     

Peritraumatic dissociation and posttraumatic stress in male Vietnam theater veterans

OBJECTIVE: The aim of this study was to determine the reliability and validity of a proposed measure of peritraumatic dissociation and, as part of that effort, to determine the relationship between dissociative experiences during disturbing combat trauma and the subsequent development of posttraumatic stress disorder (PTSD). METHOD: A total of 251 male Vietnam theater veterans from the Clinical Examination Component of the National Vietnam Veterans Readjustment Study were examined to determine the relationship of war zone stress exposure, retrospective reports of dissociation during the most disturbing combat trauma events, and general dissociative tendencies with PTSD case determination. RESULTS: The total score on the Peritraumatic Dissociation Experiences Questionnaire--Rater Version was strongly associated with level of posttraumatic stress symptoms, level of stress exposure, and general dissociative tendencies and weakly associated with general psychopathology scales from the MMPI-2. Logistic regression analyses supported the incremental value of dissociation during trauma, over and above the contributions of level of war zone stress exposure and general dissociative tendencies, in accounting for PTSD case determination. CONCLUSIONS: These results provide support for the reliability and validity of the Peritraumatic Dissociation Experiences Questionnaire--Rater Version and for a trauma-dissociation linkage hypothesis: the greater the dissociation during traumatic stress exposure, the greater the likelihood of meeting criteria for current PTSD.     

Investigation of factors responsible for the development of boar taint

The objective of this study was to evaluate the effect of 16-androstene steroids, skatole, size of accessory sexual glands and live weight on the development of boar taint in entire male pigs. In Trial I, 35 Yorkshire entire males were slaughtered at 116 ± 3.0 kg live weight. Levels of 16-androstene steroids in the salivary gland (STs), 16-androstene steroids in the fat (STf), skatole in the fat (SK), length of the bulbourethral gland (BG) and weight of the salivary gland (SG) were 44.2 ± 4.7 μg/g, 0.47 ± 0.06 μg/g, 0.20 ± 0.03 μg/g, 11.7 ± 2.2 cm and 63.50 ± 6.73 g, respectively. Samples of loin chops from the animals were evaluated by a trained sensory panel for the presence of boar odour and boar flavour. Sensory scores were correlated with all the investigated factors (P 0.05). Boar odour was particularly well correlated with SG (r = 0.61) and BG (r = 0.60); the correlation with STs was r = 0.53, with SK was r = 0.46 and with STf was r = 0.44. Similar results were obtained for boar flavour. Therefore, both skatole and 16-androstene steroids had significant effects on boar taint. The best explanation of boar taint was obtained by combining measurements of skatole levels in fat and bulbourethral gland length. Trial II involved 36 Yorkshire pigs, 12 each of entire males, gilts and castrates, slaughtered at 104.6 ± 1.1, 102.8 ± 1.8 and 101.0 ± 1.6 kg, respectively. Entire males were chosen which had low levels of 16-androstene steroids (in salivary gland: 13.4 ± 1.5 μg/g; in fat: 0.49 ± 0.09 μg/g) and low levels of skatole in the fat (0.10 ± 0.01 μg/g) but long bulbourethral glands (11.3 ± 0.2 cm). Sensory evaluation performed by a trained panel revealed stronger boar odour and boar flavour from meat from entire males than from other genders (P 0.05). The present results indicate that, although both 16-androstene steroids and skatole are important, they cannot completely account for the occurrence of boar taint detected by a trained sensory panel. Other factors, due to sexual maturity as indicated by the length of bulbourethral gland, are involved and should be considered when estimating boar taint in entire male pigs.