1.Acute flesinoxan treatment produces a different effect on rat brain serotonin synthesis than chronic treatment: an alpha-methyl-l-tryptophan autoradiographic study.
Tohyama Y;Mück-Seler D;Diksic M Neurochem Int. 2007 Dec;51(8):486-95. Epub 2007 May 22.
5-HT(1A) receptor agonists display anxiolytic and anti-depressant properties in clinical studies. In this study, we used the alpha-[(14)C]methyl-l-tryptophan (alpha-MTrp) autoradiographic method to evaluate the effects of the 5-HT(1A) agonist, flesinoxan, on regional 5-HT synthesis in the rat brain, following acute or a 14-day continuous treatment. In the first series of experiments, flesinoxan (5mg/kg; i.p.) was administered 40min before the alpha-MTrp. It resulted in a significant increase of the arterial blood oxygen partial pressure (pO(2)) and a reduction of the regional rate of 5-HT synthesis throughout the brain, with the exception of a few regions (medial geniculate body and thalamus). In the second series of experiments, flesinoxan (5mg/kgday) was administered for 14 days, using an osmotic minipump implanted subcutaneously. When compared to rats treated with saline, there was an overall significant (p<0.05) reduction in the synthesis (one-sample two-tailed t-test). However, there was no significant influence on the 5-HT synthesis rate in the dorsal and median raphe nuclei and the majority of their projection areas. A significant (p<0.05) reduction was observed in the nucleus raphe magnus, medial caudate, ventral thalamus, amygdala, ventral tegmental area, medial forebrain bundle, nucleus accumbens, medial anterior olfactory nucleus and superior olive.
2.Continuous ethanol administration influences rat brain 5-hyroxytrytamine synthesis non-umiformly: alpha-[14C]methyl-L-trytophan autoradiographic measurements.
Yamane F;Tohyama Y;Diksic M Alcohol Alcohol. 2003 Mar-Apr;38(2):115-20.
AIMS: ;The influence of alcohol on the brain serotonergic system has been studied for several decades with some discordant results. The effects of continuous and constant treatment with ethanol on the rates of serotonin [5-hydroxytryptamine (5-HT)] synthesis in discrete regions of the rat brain were studied.;METHODS: ;5-HT synthesis rates were measured using the alpha-[(14)C]methyl-l-tryptophan autoradiographic method. The rats in the experimental group were treated with 50% ethyl alcohol and those in the control group received distilled water. The fluid was delivered subcutaneously by implanted osmotic mini-pumps for 14 days at the rate of 5 micro l/h or 0.12 ml/day (0.06 ml of alcohol per day).;RESULTS: ;Chronic ethanol treatment, as delivered in the present experiment, induced a significant increase in the rate of 5-HT synthesis in descending serotonergic cell bodies (raphe pallidum, raphe obscurus, raphe magnus), nigrostriatal structures, the hippocampus and cortices. No significant changes were observed in the dorsal and median raphe nuclei or pineal body. The results suggest that there may be differences in the regulation of 5-HT synthesis in different brain structures after 14 days of continuous (subcutaneous) injection of 50% alcohol.
3.Neuroradiological assessment of brain structure and function and its implication in the pathogenesis of West syndrome.
Juhász C;Chugani HT;Muzik O;Chugani DC Brain Dev. 2001 Nov;23(7):488-95.
Neuroimaging studies with magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning have contributed significantly to our understanding of West syndrome. Cortical dysplastic lesions are the most common abnormalities seen with MRI in infants with spasms, but other structural lesions are also detected occasionally. An underlying cortical dysplasia may not be apparent until myelination has advanced in the brain and poor gray-white matter differentiation becomes observable. Many cortical dysplastic lesions can only be detected using PET scanning of glucose metabolism or gamma-aminobutyric acid(A) (GABA(A)) receptor binding. The MRI and PET findings, together with neurophysiological observations, strongly suggest that infantile spasms are initiated as cortical epileptic discharges that, during a 'critical' developmental period, may undergo secondary generalization in an age-dependent mechanism to emerge as spasms. The onset of spasms often coincides with the functional maturation of cerebral cortex. Based on data from glucose metabolism PET scanning as well as electrophysiological and neurochemical findings on infants with spasms, we have postulated that the offending lesion is a focal or diffuse cortical abnormality which, at a critical stage of maturation, causes abnormal functional interactions with brainstem raphe nuclei which project widely throughout the brain.
