Metabolism In Rat Brain Research Articles

Noninvasive demonstration of in vivo 3-fluoro-3-deoxy-D-glucose metabolism in rat brain by 19F nuclear magnetic resonance spectroscopy: suitable probe for monitoring cerebral aldose reductase activities.

The metabolism of 3-fluoro-3-deoxy-D-glucose (3-FDG) in rat brain in vivo was investigated noninvasively using 19F nuclear magnetic resonance (NMR) spectroscopy. Following an intravenous infusion of 3-FDG, 400 mg/kg, four resonances assigned to the alpha and beta anomers of 3-FDG, 3-fluoro-3-deoxy-D-sorbitol, and 3-fluoro-3-deoxy-D-fructose were clearly resolved in brain, a result indicating that 3-FDG is metabolized primarily into the aldose reductase sorbitol (ARS) pathway. An orally administered aldose reductase inhibitor, sorbinil, caused reduction of the flux of 3-FDG into the ARS, an observation suggesting that the method can be applied in quantitative studies of ARS pathway activities. Studies of 24-h urine specimens showed that in addition to the two metabolites observed in brain, F- was excreted into the urine. 3-FDG appears to be a suitable metabolic probe for assessing glucose metabolism in the ARS pathway by in vivo 19F NMR spectroscopy.

Alterations in regional energy metabolism in rat brain produced by small and by large doses of apomorphine: possible relations to autoreceptors

Dose-dependent changes in behavioural patterns and in local cerebral glucose utilization (LCGU) following subcutaneous application of apomorphine were measured in conscious, unrestrained rats by means of a scoring system and of the autoradiographic [C 14]2-deoxyglucose technique, respectively. The behavioural patterns of akinesia, ptosis, yawning and penile erections were scored. Akinesia and ptosis were most prominent after 0.02 and 0.07 mg/kg apomorphine but not after 0.18 mg/kg. Maximal scores for yawning and penile erections were obtained after 0.07 mg/kg. LCGU was not significantly changed after 0.07 mg/kg except for decreases in the cingulate cortex and hypothalamus. Apomorphine 0.5 mg/kg decreased LCGU in the cingulate, parietal and occipital cortex, anteromedial and lateral thalamus and lateral habenula but increased it in lamine IV and VI of the sensorimotor cortex, in the parafascicular nucleus of the thalamus, and in some parts of the basal ganglia and related nuclei. Similar changes in LCGU occurred after 2.0 mg/kg apomorphine, which also increased LCGU in the ventral tegmental area. The lower dose did not produce changes in LCGU opposite to those occurring after larger doses. The data obtained with LCGU do not support the idea that behavioural effects after low doses of apomorphine are elicited by activation of dopamine autoreceptors.

Effects of aldehyde dehydrogenase inhibitors on hexobarbital sensitivity and neuroamine metabolism in rat brain

Several authors have found that the aldehyde dehydrogenase (ALDH) inhibitor, disulfiram, prolongs hexobarbital-induced anaesthesia. It was suggested that this effect was caused by an alteration of the serotonergic system in brain, mediated by elevated levels of biogenic aldehydes. In the present study, disulfiram (300 mg/kg) was found to cause a 4-fold prolongation of hexobarbital-induced anaesthesia, while coprine (another potent ALDH-inhibitor) had no effect. This strongly suggested that biogenic aldehydes were not involved in this effect of disulfiram. The hexobarbital concentration in brain, at the electroencephalogram (EEG) criteria used for measuring hexobarbital sensitivity, was unaffected in rats given 75–300 mg/kg disulfiram, indicating that factors other than an increased brain hexobarbital sensitivity were responsible for the prolonged anaesthesia. Also 10–100 mg/kg coprine did not affect hexobarbital sensitivity measured this way. No alteration of the dopamine level in brain was found in rats given disulfiram, and in both disulfiram- and coprine-treated rats, similar changes in the serotonergic system were found. However, the level of norepinephrine was decreased in brains of disulfiram-treated rats, but it was unaffected by coprine. Thus, norepinephrine may have been involved in the prolongation of hexobarbital-induced anaesthesia caused by disulfiram.

Alteration of catecholamine metabolism in rat brain produced by inhalation exposure to methyl bromide.

Alteration of catecholamine metabolism in rat brain produced by inhalation exposure to methyl bromide.

Is 3,4-dihydroxyphenylglycol the major route of central norepinephrine metabolism in rat brain?

Central norepinephrine (NE) metabolism was assessed by measuring 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and 3,4-dihydroxyphenylethyleneglycol (DHPG) in different rat brain areas after saline or probenecid (300 mg/kg) administration. Under probenecid, results showed an increased accumulation of total MHPG and DHPG, and a clear preponderance of DHPG levels over MHPG in almost all the brain areas examined. Estimation of their formation rates confirmed that in basal conditions DHPG is formed more rapidly. This study supports the notion that, without ruling out the importance of MHPG, brain DHPG may be a useful index of central NE activity.

N-Acylethanolamine phospholipid metabolism in normal and ischemic rat brain

N-Acetylethanolamine phospholipids accumulate in rat brain during post-decapitative ischemia. Small amounts of these phospholipids consisting primarily of diacyl and alkenylacyl species can be detected within 15 min of ischemia and they increase linearly for 60 min. This ischemia-induced synthesis is more pronounced in developing rat brain (approx. 5.0 nmol/h per μmol lipid P) than in adult brain (0.4 nmol). Pulse labeling experiments with subcellular preparations of 10-day-old rat brain indicate a precursor-product relationship between ethanolamine phospholipids and their N-acyl analogs. N-Acylation of endogenous substrates occurs with both microsomes and mitochondria, exhibits a pH optimum of 10 and requires 1 mM Ca 2+ for maximal (0.2 mM Ca 2+ for half maximal) activity. Cell-free preparations of both developing and adult rat brain contain a phosphodiesterase which hydrolyzes N-acylphosphatidylethanolamine to phosphatidic acid and N-acylethanolamine. The latter is further hydrolyzed to fatty acid and ethanolamine by an amidohydrolase. [1- 3H]Ethanolamine, injected intracerebrally or intraperitoneally into 13- and 18-day-old rats, is incorporated into brain ethanolamine phospholipids. Since small amounts of radioactivity are also associated with N-acylethanolamine phospholipids 5 and 24 h after injection of the substrate, it appears that these phospholipids may occur at a very low level as a natural lipid constituent of rat brain.

Energy metabolism in rat brain in vivo studied by 31P nuclear magnetic resonance: Changes during postnatal development

The energy metabolism in rat brains during postnatal development was followed by in vivo 31P NMR. Using a small surface coil (from several to 10 mm in diameter) placed at the head of a conscious rat, high-energy phosphate compounds in the brain and the steady-state kinetics among them were measured. The cellular contents of some phosphate compounds changed widely during the period of postnatal cell growth from age 10 to 20 days. During the same period, the cellular activity of creatine kinase increased by a factor of more than 5 as measured by a saturation transfer technique. The in vivo value of the creatine/creatine phosphate ratio was estimated from the in vitro value (in perchloric acid extracts), assuming that the in vivo ratio of the creatine and creatine phosphate pool over the ATP and ADP pool was the same as the corresponding in vitro value. From the creatine/creatine phosphate ratio thus obtained, the value of the cytosolic ATP/ADP ratio was estimated for brains of adult rats and neonate rats. Unexpectedly the value in the latter was found to be smaller.

Acute and short-term effects of lithium on glutamate metabolism in rat brain

Amino acids of the glutamate family, viz. glutamic acid, aspartic acid, glutamine, γ-aminobutyric acid (GABA) and alanine, along with the activities of glutamic acid dehydrogenase (GDH), aspartic acid aminotransferase (AST), alanine aminotransferase (ALT), glutamine synthetase (GS), glutaminase, glutamic acid decarboxylase (GAD) and GABA-aminotransferase (GABA-T) were estimated in cerebral cortex, cerebellum and brain stem of rats treated with a single dose of lithium or with seven daily doses of lithium (3 m-equiv./kg body wt). The levels of GABA were found to increase in cerebral cortex and brain stem following the administration of a single dose and also were found to be increased in cerebral cortex and cerebellum after treatment for 7 days. The content of glutamic acid was increased in all three brain regions after treatment for 7 days. Glutamine was increased in both cerebral cortex and brain stem after treatment for 7 days, whereas aspartic acid was increased in brain stem after both the administration of single dose and treatment for 7 days. A significant increase (P < 0.05) in the activity of GS was observed in brain stem after 7 days of treatment. Similarly, a significant increase (P < 0.01) in the activity of AST was observed in all three regions of the brain following the treatment for 7 days. The above results are discussed in relation to the known effects of lithium on brain cation metabolism and a suggestion is made that an imbalance in the functional activities of glutamic acid and GABA as a result of quantitative changes in these amino acids, brought about by lithium, may play a role in the therapeutic efficacy of lithium in bipolar disorders.

Polychlorinated biphenyls produce regional alterations of dopamine metabolism in rat brain

Adult male rats were gavaged with a mixture of polychlorinated biphenyls (PCBs; Aroclors 1254 and 1260) at either 500 or 1000 mg/kg body weight. Concentrations of dopamine (DA) and its major metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were determined in caudate nucleus and lateral olfactory tract on postgavage Days 1, 3, 7 and 14. DA and DOPAC concentrations in caudate decreased after exposure to PCBs, as did HVA/DA ratios. DA concentrations in the lateral olfactory tract were unaffected, although DOPAC/DA ratios decreased. These results demonstrate that the mature mammalian nervous system is sensitive to a brief exposure to PCBs and that regional differences exist in the neurochemical sequelae of exposure to PCBs.

Effects of hypoxia on rat brain metabolism: Unilateral in vivo carotid infusion

An in vivo brain perfusion technique was used to examine effects of hypoxia on cerebral cortical metabolism in barbiturate-anesthetized rats. Dulbecco's phosphatebuffered solution (PBS), or Dulbecco's PBS + 6 m M glucose, was infused into the right carotid circulation for 0 to 3 min, at a rate that reduced regional cerebral blood flow to the ipsilateral parietal lobe by more than 40% and O 2 delivery by about 50%. The duration of infusion of either solution was correlated negatively with the ipsilateral parietal lobe concentrations of glucose, ATP, and phosphocreatine (PCr), and positively with parietal concentrations of lactate and cAMP. cGMP increased in relation to infusion duration of Dulbecco's PBS. Statistically significant elevations of brain lactate occurred after 1 min of infusion of Dulbecco's PBS; lactate was elevated and glucose was reduced after 2 min of infusion of either solution. Brain ATP, PCr, and glycogen concentrations decreased in relation to the elevation in brain lactate, and the [PCr]:[ATP] ratio declined. The results demonstrated that limited hypoxia stimulated cerebral glycolysis and produced a concurrent decrease in brain ATP and PCr. However, ATP was spared to a degree, at the expense of PCr.

Selective activation of mesolimbic and mesocortical dopamine metabolism in rat brain by infusion of a stable substance P analogue into the ventral tegmental area

Microinfusion of the metabolically stable substance P (SP) agonist, [pGlu 5, MePhe 8, Sar 9]-SP 5–11 (DiMe-C7), into the ventral tegmental area (VTA) of rat brain increased levels of the dopamine (DA) metabolite dihydroxyphenylacetic acid in the prefrontal cortex (+120%) and nucleus accumbens (+30%) but not in other regions of forebrain. In contrast, infusions of DiMe-C7 or SP into the lateral ventricles or microinfusions of SP into VTA failed to elicit increases DOPAC levels in forebrain. DA levels were unaffected by SP or DiMe-C7 regardless of the route administration. These data and previous studies suggest a role for endogenous SP in the modulation of mesocotical and mesolimbic DA neurones.

The effect of single and repeated administration of bromocriptine on monoamine metabolism in rat brain and [3H]spiroperidol binding to striatal membranes.

Administration of a single high dose of bromocriptine decreased synthesis and release of dopamine and serotonin in several brain regions, most notably in the striatum. Bromocriptine modified the kinetics of [3H]spiroperidol binding to striatal membranes, but these changes were not prominent 2 h after injection when modifications of monoamine metabolism were evaluated. After injection of the same dose of bromocriptine daily for 10 days, the decrease in dopamine synthesis persisted, while other aspects of monoamine metabolism, presumably controlled by dopamine autoreceptors, returned to normal values. This adaptation was not caused by decreased blood levels of bromocriptine, since bromocriptine accumulated in plasma after repeated drug administration. This study provides evidence that different aspects of dopamine cell function, presumably controlled by autoreceptors, show different patterns of adaptation after chronic administration of dopamine agonists.

The effects of L-threo-dihydroxyphenylserine on norepinephrine metabolism in rat brain

The effects of L- threo-3,4-dihydroxyphenylserine (DOPS), an artificial precursor of norepinephrine (NE), on NE metabolism in rat brain were investigated. DOPS administration resulted in a significant elevation in cerebral NE and 3-methoxy-4-hydroxyphenylglycol contents, while carbidopa pretreatment completely blocked these increases. After brain NE was depleted by either α-methyl- p-tyrosine (AMPT), fusaric acid, FLA-63, or reserpine, NE restoration by DOPS was observed in rats treated with either fusaric acid or chronic reserpine. No NE restoration was observed after pretreatment with AMPT, FLA-63, or acute reserpine. The results suggest that NE formed after DOPS administration is mainly localized in the brain capillaries. In some NE-depleting conditions, however, DOPS can penetrate the brain parenchyma.

α 1-Adrenergic receptors and stimulation of [ 3H]inositol metabolism in rat brain: Regional distribution and parallel inactivation

The relationship between norepinephrine-stimulated phosphatidyl-inositol metabolism and α 1-adrenergic receptor density was examined in rat brain. Increases in phosphatidyl-inositol metabolism were determined by accumulation of [ 3H]inositol phosphates in the presence of lithium in brain slices, while receptor density was determined by specific binding of 125I-BE 2254 ( 125IBE) in membrane fractions. Treatment of slices of cerebral cortex with increasing concentrations of the irreversible α 1-adrenergic receptor antagonist phenoxybenzamine caused a parallel inactivation of specific 125IBE binding sites and norepinephrine-induced [ 3H]inositol phosphate accumulation, although approximately 20% of the binding sites remained after abolition of the inositol response. Comparison of the density of 125IBE binding sites and the magnitude of norepinephrine-stimulated [ 3H]inositol phosphate accumulation in 8 different brain regions did not show a particularly good correlation. The thalamus had the highest density of binding sites and an intermediate inositol response, while the hippocampus had the highest inositol response but an intermediate density of binding sites. However, the cerebellum had the lowest density of binding sites and no measurable inositol response. Treatment of slices of each region with 300 nM phenoxybenzamine abolished the inositol response and caused a 59–73% decrease in the density of 125IBE binding sites. The lack of correlation between receptor density and inositol response between brain regions could not be explained on the basis of receptor affinity, spare receptors, protein content, nor differences in slice size. These results suggest that α 1-adrenergic receptors labeled by 125IBE are coupled to [ 3H]inositol metabolism in rat brain, but the receptor density is not the sole determinant of the magnitude of norepinephrine-induced increases in [ 3H]inositol metabolism.

Changes of enzymes involved in prostaglandin metabolism and prostaglandin binding proteins in rat brain during development and aging.

In the developing rat brain, the enzymatic formation of prostaglandin D2 from prostaglandin H2 increased 60-fold from day 12 of gestation to birth. The activity still rose gradually to the highest level (90 nmol/min/g wet tissue) at day 7 after birth. The activities of prostaglandin E2 and F2 alpha synthetases in rat brain were highest at gestational age 19 days (30 nmol/min/g wet tissue), respectively. The specific activity of NADP-dependent 15-hydroxy-prostaglandin D2 dehydrogenase in rat brain was highest at the earliest gestational age we examined (day 12 of gestation). The specific bindings of prostaglandin D2 and E2 to the crude mitochondrial fraction of rat brain were observed from day 16 of gestation and increased to day 7 after birth. Although the activities of the enzymes responsible for prostaglandin metabolism were unchanged postmaturationally, the maximal concentrations of the binding sites on the synaptic membrane for both prostaglandins D2 and E2 decreased with constant affinity to less than one-sixth with age from 1 week to 24 months after birth. These results indicate that prostaglandins may play important roles during maturation and aging in rat brain.

Modulation of the activity of purified phosphatidylinositol 4-phosphate kinase by phosphorylated and dephosphorylated B-50 protein

To investigate the modulation of phosphatidylinositol 4-phosphate kinase activity by the degree of phosphorylation of the B-50 protein, the enzyme was purified from rat brain cytosol by ammonium sulphate precipitation and DEAE-cellulose column chromatography. Purified rat brain B-50 was phosphorylated with protein kinase C and dephosphorylated with alkaline phosphatase. Incubation of the semi-purified phosphatidylinositol 4-phosphate kinase with 1 μg of the B-50 preparation enriched in the dephospho-form, resulted in a small reduction of phosphatidylinositol 4-phosphate kinase activity (−16%), whereas incubation with the phospho B-50 preparation inhibited the enzyme activity by 40%. The effect of exogenous B-50 was studied in the presence of 10 μg albumin to minimize aspecific protein-protein interactions. The present data on the effect of exogenous B-50 protein on phosphatidylinositol 4-phosphate kinase activity, further support our hypothesis that the phosphorylation state of B-50 may be a regulatory factor in phosphoinositide metabolism in rat brain.

Metabolism during fetal life: a functional assessment of metabolic development.

Metabolism during fetal life: a functional assessment of metabolic development.C T Jones, and T P RolphC T Jones, and T P RolphPublished Online:01 Apr 1985https://doi.org/10.1152/physrev.1985.65.2.357MoreSectionsPDF (13 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByGuinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic30 May 2018 | The Journal of Physiology, Vol. 596, No. 23Cortisol advantage of neighbouring the opposite sex in utero5 September 2018 | Royal Society Open Science, Vol. 5, No. 9Maturation of Cardiac Energy Metabolism During Perinatal Development19 July 2018 | Frontiers in Physiology, Vol. 9Metabolic Coordination of Physiological and Pathological Cardiac RemodelingCirculation Research, Vol. 123, No. 1Modelling ischemia-reperfusion injury (IRI) in vitro using metabolically matured induced pluripotent stem cell-derived cardiomyocytesAPL Bioengineering, Vol. 2, No. 2Pregnancy-induced changes in the circadian expression of hepatic clock genes: implications for maternal glucose homeostasisMichaela D. Wharfe, Caitlin S. Wyrwoll, Brendan J. Waddell, and Peter J. Mark1 September 2016 | American Journal of Physiology-Endocrinology and Metabolism, Vol. 311, No. 3Developmental regulation of key gluconeogenic molecules in nonhuman primates18 December 2014 | Physiological Reports, Vol. 2, No. 12Energy metabolism in mammalian brain during developmentProgress in Neurobiology, Vol. 73, No. 6Glucose-insulin infusion improves cardiac function during fetal tachycardiaJournal of the American College of Cardiology, Vol. 43, No. 3Magnetic resonance proton spectroscopy and diffusion weighted imaging of chick embryo brain in ovoDevelopmental Brain Research, Vol. 141, No. 1-2Improving Energy Metabolism in the Postischemic Heart-The Story of GIK17 August 2016 | Seminars in Cardiothoracic and Vascular Anesthesia, Vol. 7, No. 1Ontogeny of malate-aspartate shuttle capacity and gene expression in cardiac mitochondriaThomas D. Scholz, Stacia L. Koppenhafer, Cynthia J. Teneyck, and Brian C. Schutte1 March 1998 | American Journal of Physiology-Cell Physiology, Vol. 274, No. 3Distribution of lactate dehydrogenase isoenzymes in coelomic fluid and fetal adnexaePlacenta, Vol. 17, No. 5-6Insulin and glucose modulate glucose transporter messenger ribonucleic acid expression and glucose uptake in trophoblasts isolated from first-trimester chorionic villiAmerican Journal of Obstetrics and Gynecology, Vol. 173, No. 4Differential effects of hypoxia on electrical and mechanical activities of isolated ventricular muscles from fetal and adult guinea-pigsGeneral Pharmacology: The Vascular System, Vol. 25, No. 1Perinatal adaptation in animalsAnimal Reproduction Science, Vol. 28, No. 1-4Effects of hypoxia on fetal rat brain metabolism studied in utero by31P-NMR spectroscopyBrain Research, Vol. 551, No. 1-2Growth of the rat foetal liver in gestational diabetesComparative Biochemistry and Physiology Part A: Physiology, Vol. 99, No. 3A sensitive period in gestation for nicotine acceleration of neuromuscular maturationInternational Journal of Developmental Neuroscience, Vol. 9, No. 3Accelerated neuromuscular development in the rat with prenatal exposure to nicotineInternational Journal of Developmental Neuroscience, Vol. 8, No. 5Oxidative influence on development and differentiation: An overview of a free radical theory of developmentFree Radical Biology and Medicine, Vol. 6, No. 6Changes in protein turnover and growth of the rat lung in response to ageing and long-term dietary restrictionMechanisms of Ageing and Development, Vol. 42, No. 3Some aspects of amino acid metabolism in the rat fetusComparative Biochemistry and Physiology Part B: Comparative Biochemistry, Vol. 88, No. 3 More from this issue > Volume 65Issue 2April 1985Pages 357-430 Copyright & PermissionsCopyright © 1985 by American Physiological Societyhttps://doi.org/10.1152/physrev.1985.65.2.357PubMed3885272History Published online 1 April 1985 Published in print 1 April 1985 Metrics

Effects of systemically administered lithium on phosphoinositide metabolism in rat brain, kidney, and testis.

A single subcutaneous dose of 10 mEq/kg LiCl gives rise to an increase in the cerebral cortex level of myo-inositol-1-P (I1P) that closely follows cortical lithium levels and, at maximum, is 40-fold above the control value. Kidney and testis show smaller increases in I1P level following LiCl administration. The I1P level is still sixfold greater than that of untreated rat cortex 72 h later. In cortex, parallel increases also occur in myo-inositol-4-P (I4P) and myo-inositol 1,2-cyclic-P (cI1,2P), whereas myo-inositol-5-P (I5P) remains unchanged. The cortical increases in I1P and I4P levels are partially reversed by administering 150 mg/kg of atropine 22 h after the LiCl, treatment that does not affect cI1,2P. When doses of LiCl from 2 to 17 mEq/kg are given, the cerebral cortex levels of I1P and myo-inositol, measured 24 h later, are found to reach a plateau at about 9 mEq/kg of LiCl, whereas cortical lithium levels continued to increase with greater LiCl doses. Levels of all three of the brain phosphoinositides are unchanged by the 10 mEq/kg LiCl dose, as is the uptake of 32Pi into these lipids. Chronic dietary administration of LiCl for 22 days showed that the effects of lithium on I1P and myo-inositol levels persist for that period. Over the course of the chronic administration of the lithium, levels of I1P, myo-inositol, and of lithium in cortex remained significantly correlated. We believe that these increases in inositol phosphates result from endogenous phosphoinositide metabolism in cerebral cortex and that lithium is capable of modulating that metabolism by reducing cellular myo-inositol levels. The size of the effect is a function of both lithium dose and the degree of stimulation of receptor-linked phosphoinositide metabolism. This property of lithium may explain part of its ability to moderate the symptoms of mania. Our chronic study suggests that prolonged administration of LiCl does not result in compensatory changes in myo-inositol-1-P synthase or myo-inositol-1-phosphatase.

Effects of rolipram, a novel antidepressant, on monoamine metabolism in rat brain.

The phosphodiesterase inhibitor and putative antidepressant rolipram (0.3-30 mg/kg i.p.) stimulated the accumulation of dopa following inhibition of the aromatic amino acid decarboxylase with 3-hydroxybenzylhydrazine HCl dose-dependently in all brain regions investigated, suggesting that both dopamine and noradrenaline synthesis was enhanced. The stimulatory effect of rolipram on dopa accumulation in dopamine rich regions persisted even after pretreatment with gamma-butyrolactone which by itself increased dopa accumulation three fold. Following inhibition of catecholamine synthesis with alpha-amethyl-p-tyrosine rolipram accelerated the disappearance of noradrenaline and slowed the disappearance of dopamine. At low doses rolipram tended to reduce the pargyline-induced accumulation of 3-methoxytyramine. Rolipram attenuated the accumulation of 5-hydroxytryptophan in the neocortex and the diencephalon of 3-hydroxybenzylhydrazine HCl pretreated rats. The data suggest that rolipram enhances noradrenergic transmission by direct stimulation of tyrosine hydroxylase and by an increase of neuronal activity. Despite a stimulatory effect on tyrosine hydroxylase rolipram does not appear to alter dopamine release and metabolism to a large extent. In view of the occurrence of head-twitches the rolipram-induced reduction of 5-hydroxytryptamine metabolism may be due to feedback inhibition.

Effects of short- and long-term protriptyline treatment on phospholipid metabolism in rat brain.

Wistar rats were injected intraperitoneally with 10 mg/kg of protriptyline according to one of the following schedules: a single dose or daily for 4 days (short-term), or daily for 2 or 13 weeks (long-term). Total lipid, total phospholipid, and individual phospholipid contents in the brain were determined. Further, the incorporation of 32P into individual phospholipids in vivo and the fatty acid composition of phosphatidylethanolamine in the brains of rats treated with protriptyline for 13 weeks were studied. Three alternative phases of changes of total and individual phospholipid contents in the brain during 13 weeks of experimentation were distinguished. An increase of phospholipid contents after 4 days, a decrease after 2 weeks, and a further increase after 13 weeks of protriptyline administration were found. However, phosphatidylinositol and phosphatidic acid levels after 13 weeks of protriptyline administration were diminished. The decrease of specific radioactivity of phosphatidylethanolamine, phosphatidylcholine, and phosphatidylserine and the increase of phosphatidylinositol, phosphatidic acid, and sphingomyelin in rats treated with the drug for a longer period of time were noted. No greater differences in fatty acid composition of phosphatidylethanolamine in the brains of the same group of rats were observed as compared to control. These results indicate that during long-term treatment with protriptyline the contents of lipids and phospholipids in rat brain are altered. The modification of the biological function of phospholipids in brain cell membranes is suggested.