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Distribution of the hallucinogens N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine in rat brain following intraperitoneal injection: application of a new solid-phase extraction LC-APcI-MS-MS-isotope dilution method.

A method for the solid-phase extraction (SPE) and liquid chromatographic-atmospheric pressure chemical ionization-mass spectrometric-mass spectrometric-isotope dilution (LC-APcI-MS-MS-ID) analysis of the indole hallucinogens N,N-dimethyltryptamine (DMT) and 5-methoxy DMT (or O-methyl bufotenin, OMB) from rat brain tissue is reported. Rats were administered DMT or OMB by the intraperitoneal route at a dose of 5 mg/kg and sacrificed 15 min post treatment. Brains were dissected into discrete areas and analyzed by the methods described as a demonstration of the procedure's applicability. The synthesis and use of two new deuterated internal standards for these purposes are also reported.

Animals↗

Intraventricular macrophages in the lateral ventricles with special reference to epiplexus cells: a quantitative analysis and their uptake of fluorescent tracer injected intraperitoneally in rats of different ages.

The labelling of epiplexus cells associated with the choroid plexus in the lateral ventricles was examined in rats of different ages with the fluorescent dye, rhodamine isothiocyanate (RhIc). A quantitative study was also attempted; this showed that the number of epiplexus cells and their related cells, namely supraependymal and free-floating cells, increased with age. The mean absolute number of epiplexus cells ranged from approximately 700 in the newborn to approximately 2200 in rats of 17 d of age; thereafter it remained unchanged. The number of free-floating cells also increased substantially but showed considerable individual variation. Following i.p. injection, the tracer was rapidly taken up by the epiplexus cells. This provided strong support for their phagocytic nature. In the newborn (1 d) and developing (13 d, 17 d) rats, RhIc-labelled epiplexus cells were first observed 3 h after the injection. In adult rats, labelled cells were not observed until 12 h after injection. In either case, the fluorescence in the epiplexus cells gradually increased with time. It is suggested from this study that the blood-CSF barrier in the choroid plexus in postnatal rats is incomplete, thereby allowing a rapid transvascular diffusion of the injected RhIc into the blood circulation. The fluorescent dye which enters the ventricle by way of the choroid epithelium is subsequently taken up by the epiplexus cells. Such an unimpeded passage, however, is reduced in the adult rats, probably due to the maturation of the blood capillaries as well as the choroid epithelium.

Aging↗

The effect of intraperitoneal injection of GABA or GHBA on monoamine histofluorescence in the rat brain.

Using the Falck-Hillarp histofluorescence method we studied the effect of gamma-aminobutyric acid (GABA) or gamma-hydroxybutyric acid (GHBA) on catecholaminergic (CA) and serotoninergic (5-HT) neurons in the rat brain. Both GABA as well as GHBA enhanced the CA fluorescence in noradrenergic (NA) terminals in the cerebellar cortex, which suggested that the NA content increased in these terminals. GHBA but not GABA also enhanced the fluorescence in dopaminergic (DA) terminals in the neostriatum and limbic structures. No significant changes of fluorescence were found in 5-HT neurons after both compounds. The results obtained suggest that, apart from the known GABA-DA interaction, there exists also a GABA-NA interaction in the cerebellar cortex.

Animals↗

Adaptive changes of rat liver cells induced by repeated intraperitoneal injections of d-galactosamine. III-Light- and electron-microscopic investigations of hepatocellular cytoplasmic changes.

In rats hepatocellular cytoplasmic changes after daily repeated D-galactosamine (GalN) intoxication--i.e. subacute GalN intoxication--were studied by light and electron microscopy. The number of GalN injections--and thus the days of survival--was between one and 30. The rats were killed six hours after the last GalN injection. Less degenerative changes were found after repeated GalN injections. An increased formation of atypical dense bodies (ADB), a temporary pronounced lipid accumulation and changes of the rough and smooth endoplasmic reticulum were prominent features of subacute GalN intoxication. The implications with respect to a modified GalN action in subacute GalN intoxication are discussed with special reference to biochemical data obtained in the same experimental model (Schuchhardt et al., 1977).

Adaptation, Physiological↗

Absence of central nervous system pathology in severe combined immunodeficiency mice intraperitoneally injected with peripheral blood lymphocytes from multiple sclerosis patients.

In order to reproduce some of the pathological features of multiple sclerosis (MS) we transplanted peripheral blood lymphocytes (PBLs) from seven patients with MS into the peritoneal cavity of 28 severe combined immunodeficiency (MS-SCID) mice. Seven SCID mice were also transplanted with PBLs from two healthy subjects (hu-SCID). Animals were sacrificed between 2 and 8 weeks after transplantation (a.t.). Polymerase chain reaction (PCR) using primers able to amplify the HLA-DQ alpha region showed presence of human cells in neural tissues of MS-SCID mice. Immunocytochemical analysis revealed the scattered appearance of human lymphocytes (mostly CD45RO+ T cells) in the meningeal space and choroid plexuses of MS-SCID brains. However, human lymphocytes were similarly found in brains of hu-SCID mice. Both groups of mice never showed signs or symptoms of neurological impairment. Our results indicate that the simple transplantation of lymphocytes from MS patients into SCID mice is not likely to produce an MS-like pathology.

Animals↗

Time-dependent alterations of leukotriene production and catabolism in rat peritoneal macrophages following intraperitoneal injection of thioglycollate broth.

Alterations of leukotriene (LT) productivity in peritoneal macrophages (PM) from untreated rats (control) as well as from rats treated i.p. with thioglycollate broth (TG) were investigated on days 3, 7 and 14 after TG administration. The resident PM from the untreated rats produced mainly LTB4 and 5-HETE with small amounts of 12-HETE and LTD4 with only a trace of LTC4 when stimulated with the calcium ionophore A23187. The PM elicited from rats on days 3 and 7 produced more LTC4 than did the resident PM but fewer other lipoxygenase metabolites. On day 14, however, the elicited PM resembled the resident PM in terms of lipoxygenase metabolite production. Similar results were achieved in the presence of arachidonic acid and A23187. A decrease in lipoxygenase metabolism in the elicited PM was also suggested by using opsonized zymosan. Catabolism studies indicated a reduction in r-glutamyl transpeptidase activity in the elicited PM and suggested a reduction in catabolism for LTB4 in the former cells. The authors conclude that the TG-elicited PM generate fewer lipoxygenase metabolites than the resident PM following stimulation, but show a preferential conversion of LTA4 to sulfidopeptide LTs rather than to LTB4. The elicited PM also show a reduced catabolism for LTC4 and LTB4.

Animals↗