Brain Amino Acid Levels Research Articles

A chemically-induced acute model of maple syrup urine disease in rats for neurochemical studies

We report a chemically-induced model of maple syrup urine disease (MSUD) in 10- and 30-day-old rats produced by subcutaneous administration of a branched-chain amino acids (BCAA) pool along with the analyses of plasma and brain amino acid levels by HPLC at 0–120min after administration. We observed an increase of plasma leucine (Leu), isoleucine (Ile) and valine (Val) concentrations in both 10- and 30-day-old rats. These increases were accompanied by a concomitant reduction of plasma concentrations of methionine (Met), phenylalanine (Phe), tyrosine (Tyr), histidine (His), alanine (Ala), lysine (Lys), and ornithine (Orn) in 10-day-old rats and of Met, Phe, Tyr, tryptophan (Trp), and Orn in 30-day-old rats. These results are similar to those observed in MSUD patients during crises, when plasma levels of large neutral amino acids (LNAA) are also reduced when BCAA concentrations are increased. In the brain, increased concentrations of Leu, Ile and Val were achieved in 10-day-old rats at all times after injection. In contrast, no differences in cerebral concentrations of BCAA were observed in 30-day-old rats. In conclusion, the present MSUD model, using 10- rather than 30-day-old rats, has a similar amino acid profile to that of MSUD untreated patients and is suitable to investigate the mechanisms of brain damage characteristic of this disorder.

Amino acid levels in some lethargic mouse brain areas before and after pentylenetetrazole kindling

Genetic animal models have contributed significantly to our understanding of epilepsy causes. Lethargic mice are considered a valid model of absence epilepsy, which have been shown to possess behavioral, electrographic and pharmacological profiles similar to those of humans with absence epilepsies. Single gene mutations that comprise the β 4 subunit of voltage-sensitive Ca 2+ channels underlie the spontaneous discharges of the absence, non-convulsive seizures of lethargic mice. There are no available data concerning how the mutant channels actually behave at terminals in response to chemical activation by subconvulsant stimulation with pentylenetetrazole. In this study, we found no significant difference in the convulsive dose 50 between lethargic and control mice. Lethargic mice showed a more rapid development of kindling to pentylenetetrazole than control animals. No significant differences were observed between the groups of mice rechallenged with pentylenetetrazole 30 or 60 days after the end of the chronic treatment. Marked differences in brain amino acid levels were found between the two strains of mice in basal conditions and after kindling. In conclusion, our results indicate that lethargic mice show a range of biochemical and behavioral changes, correlated in particular with a higher susceptibility to develop kindled seizures.

Differential effects of the substrate inhibitor l- trans-pyrrolidine-2,4-dicarboxylate (PDC) and the non-substrate inhibitor dl-threo-β-benzyloxyaspartate ( dl-TBOA) of glutamate transporters on neuronal damage and extracellular amino acid levels in rat brain in vivo

The extracellular concentration of glutamate is highly regulated by transporter proteins, due to its neurotoxic properties. Dysfunction or reverse activation of these transporters is related to the extracellular accumulation of excitatory amino acids and neuronal damage associated with ischemia and hypoglycemia. We have investigated by microdialysis the effects of the substrate and the non-substrate inhibitors of glutamate transporters, l-trans-2,4-pyrrolidine dicarboxylate (PDC) and dl-threo-β-benzyloxyaspartate ( dl-TBOA), respectively, on the extracellular levels of amino acids in the rat hippocampus in vivo. In addition, we have studied the effect of both inhibitors on neuronal damage after direct administration into the hippocampus and striatum. Electroencephalographic activity was recorded after the intrahippocampal infusion of dl-TBOA or PDC. Microdialysis administration of 500μM dl-TBOA into the hippocampus increased 3.4- and nine-fold the extracellular levels of aspartate and glutamate, respectively. Upon stereotaxic administration it induced neuronal damage dose-dependently in CA1 and dentate gyrus, and convulsive behavior. Electroencephalographic recording showed the appearance of limbic seizures in the hippocampus after dl-TBOA infusion. In the striatum it also induced dose-dependent neuronal damage. These effects were prevented by the i.p. administration of the glutamate receptor antagonists (+)-5-methyl-10,11-dihydroxy-5 H-dibenzo( a,d)cyclohepten-5,10-iminemaleate and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo( F)-quinoxaline. In contrast to dl-TBOA, PDC (500μM) induced a more discrete elevation of excitatory amino acids levels (2.6- and three-fold in aspartate and glutamate, respectively), no neuronal damage or behavioral changes, and no alterations in electroencephalographic activity. The differential results obtained with dl-TBOA and PDC might be attributed to their distinct effects on the extracellular concentration of amino acids. Results are relevant to the understanding of the role of glutamate transporters in amino acid removal or release and the induction of excitotoxic cell death.

Effects of some synthetic kynurenines on brain amino acids and nitric oxide after pentylenetetrazole administration to rats.

We have previously proven that some synthetic kynurenines behave as antagonists of the N-methyl-d-aspartate receptor inhibiting neuronal subtype of nitric oxide synthase activity. We now investigate the anticonvulsant activity of four of these kynurenines in pentylenetetrazole (PTZ)-treated rats. The rats were treated with each kynurenine (10-160 mg/kg, s.c.) 30 min before PTZ administration (100 mg/kg, s.c.). Then, latency, duration and intensity of the first seizure and the percent animal survival were noted. PTZ-induced death was counteracted by high doses of kynurenines. Latency of the first seizure was significantly increased and its intensity reduced at the same doses, whereas the duration of the first seizure significantly decreased with doses of 20 mg/kg in most of the kynurenines tested. Three hours after PTZ administration, the surviving animals were sacrificed and the levels of brain amino acids and nitrite were measured. PTZ administration increased glutamate, glutamine, serine and taurine levels in different brain areas. High doses of kynurenines generally counteracted the effects of PTZ on excitatory amino acids, but they also reduced inhibitory aminoacids. However, the most consistent effect of kynurenines was the dose-dependent reduction of brain nitrite levels induced by PTZ. These results reveal a new family of anticonvulsant drugs that affect mainly to nitric oxide production in the brain.

Ethanol but not acetaldehyde induced changes in brain taurine: a microdialysis study.

Research has suggested that catalase plays a role in mediating ethanol's psychopharmacological effects. Catalase is an enzyme that oxidizes ethanol to acetaldehyde. It has been reported that when catalase activity is reduced by 3-amino-1,2,4-triazole (AT), rats reduce their intake and preference for ethanol. The present study assessed the effects of AT on the brain amino acids levels following ethanol administration in Wistar rats. The study consisted of three parts. In the first part, we found no effects of acute and chronic intraperitoneally administered acetaldehyde on amino acids dialysate levels in nucleus accumbens. In the second part, AT was administered five hours prior to ethanol or its vehicle. Ethanol significantly affected the levels of taurine in rat pre-treated with AT. In the final part, ethanol was administered following the pre-treatment with AT but the dependent variable was the concentration of ethanol in the brain.

Changes in brain amino acids and nitric oxide after melatonin administration in rats with pentylenetetrazole-induced seizures.

We examined the effect of melatonin on brain levels of amino acids and nitric oxide (NO) after pentylenetetrazole (PTZ)-induced seizures in rats. Animals were treated with melatonin (10-160 mg/kg, i.p.) 30 min before PTZ administration (100 mg/kg, s.c.), and were killed 3 hr later. At the dose of 80 mg/kg, melatonin significantly increased the latency (5.7-12.7 min) and decreased the duration (31.2-18.4 s) of the first seizure, reducing PTZ induced mortality from 87.5 to 25%. After kill, brains were removed and neurotransmitters and nitrite levels measured in prefrontal cortex (PF), parieto-temporal cortex (PF), striatum (ST), hippocampus (HP) and brain stem (BS) by high performance liquid chromatography. PTZ treatment increased glutamine levels in all brain areas studied, without changes in glutamate, gamma-amino butyric acid (GABA) and glycine. Aspartate and taurine increased in PF and PT and in HS and PT, respectively. Melatonin administration displayed a dose-dependent effect. At doses of 10-40 mg/kg, melatonin counteracted the PTZ-induced glutamine increase and reduced both glutamate and aspartate levels in the studied areas, with minor changes in GABA and glycine content. At doses of 80 and 160 mg/kg, the levels of glutamine, and glutamate, and to a lesser extent aspartate increased, whereas serine levels did not change. These two doses of melatonin also increased taurine, GABA and glycine in most brain areas studied. Treatment with melatonin (40-160 mg/kg) significantly decreased nitrite content in PT cortex, ST and BS areas of epileptic rats, without changes in the other brain regions. The results suggest that the anticonvulsant property of melatonin involves a modulation of both brain amino acids and NO production.

Reduction of large neutral amino acid levels in plasma and brain of hyperleucinemic rats

Neurological dysfunction is common in patients with maple syrup urine disease (MSUD). However, the mechanisms underlying the neuropathology of this disorder are poorly known. In the present study we investigated the effect of acute hyperleucinemia on plasma and brain concentrations of amino acids. Fifteen-day-old rats were injected subcutaneously with 6 μmol l-leucine per gram body weight. Controls received saline in the same volumes. The animals were sacrificed 30–120 min after injection, blood was collected and their brain rapidly removed and homogenized. The amino acid concentrations were determined by HPLC using orthophtaldialdehyde for derivatization and fluorescence for detection. The results showed significant reductions of the large neutral amino acids (LNAA) l-phenylalanine, l-tyrosine, l-isoleucine, l-valine and l-methionine, as well as l-alanine, l-serine and l-histidine in plasma and of l-phenylalanine, l-isoleucine, l-valine and l-methionine in brain, as compared to controls. In vitro experiments using brain slices to study the influence of leucine on amino acid transport and protein synthesis were also carried out. l-Leucine strongly inhibited [ 14C]- l-phenylalanine transport into brain, as well as the incorporation of the [ 14C]-amino acid mixture, [ 14C]- l-phenylalanine and [ 14C]- l-lysine into the brain proteins. Although additional studies are necessary to evaluate the importance of these effects for MSUD, considering previous findings of reduced levels of LNAA in plasma and CSF of MSUD patients during crises, it may be speculated that a decrease of essential amino acids in brain may lead to reduction of protein and neurotransmiter synthesis in this disorder.

Alteration of excitation‐contraction coupling mechanism in extensor digitorum longus muscle fibres of dystrophic mdx mouse and potential efficacy of taurine

No clear data is available about functional alterations in the calcium-dependent excitation-contraction (e-c) coupling mechanism of dystrophin-deficient muscle of mdx mice. By means of the intracellular microelectrode "point" voltage clamp method, we measured the voltage threshold for contraction (mechanical threshold; MT) in intact extensor digitorum longus (EDL) muscle fibres of dystrophic mdx mouse of two different ages: 8 - 12 weeks, during the active regeneration of hind limb muscles, and 6 - 8 months, when regeneration is complete. The EDL muscle fibres of 8 - 12-week-old wildtype animals had a more negative rheobase voltage (potential of equilibrium for contraction- and relaxation-related calcium movements) with respect to control mice of 6 - 8 months. However, at both ages, the EDL muscle fibres of mdx mice contracted at more negative potentials with respect to age-matched controls and had markedly slower time constants to reach the rheobase. The in vitro application of 60 mM taurine, whose normally high intracellular muscle levels play a role in e-c coupling, was without effect on 6 - 8-month-old wildtype EDL muscle, while it significantly ameliorated the MT of mdx mouse. HPLC determination of taurine content at 6 - 8 months showed a significant 140% rise of plasma taurine levels and a clear trend toward a decrease in amino acid levels in hind limb muscles, brain and heart, suggesting a tissue difficulty in retaining appropriate levels of the amino acid. The data is consistent with a permanent alteration of e-c coupling in mdx EDL muscle fibres. The alteration could be related to the proposed increase in intracellular calcium, and can be ameliorated by taurine, suggesting a potential therapeutic role of the amino acid.

Chronic lamotrigine treatment increases rat hippocampal GABA shunt activity and elevates cerebral taurine levels

The mechanism of action of the antiepileptic drug lamotrigine has previously been investigated only in acute experiments and is thought to involve inhibition of voltage-dependent sodium channels. However, lamotrigine is effective against more forms of epilepsies than other antiepileptic drugs that also inhibit sodium channels. We investigated whether chronic lamotrigine treatment may affect cerebral amino acid levels. Rats received lamotrigine, 10 mg/kg/day, for 90 days. The hippocampal level of GABA increased 25%, and the activities of glutamate decarboxylase and succinic semialdehyde/GABA transaminase increased 12 and 21% ( p< 0.05), respectively, indicating increased GABA turnover. The uptake of GABA and glutamate into proteoliposomes remained unaltered. The level of taurine increased 27% in the hippocampus and 16% in the frontal and parietal cortices. The activities of hexokinase and α-ketoglutarate dehydrogenase, remained at control values. Serum lamotrigine was 41.7±1.5 μM (mean±S.E.M.), which is within the range seen in epileptic patients. Acute experiments with 5, 20 or 100 mg lamotrigine/kg, caused no changes in brain amino acid levels. The results suggest that chronic lamotrigine treatment increases GABAergic activity in the hippocampus. The cerebral increase in taurine, which has neuromodulatory properties, may contribute to the antiepileptic effect of lamotrigine.

6. Effects of long-term lamotrigine and valproate treatment on brain amino acid levels and enzyme activities in male Wistar rats

6. Effects of long-term lamotrigine and valproate treatment on brain amino acid levels and enzyme activities in male Wistar rats

Depletion of brain histamine induced by α -fluoromethylhistidine enhances radial maze performance in rats with modulation of brain amino acid levels

We examined the effects of repeated administration of (S)- α- fluoromethylhistidine (FMH), a specific inhibitor of histidine decarboxylase (HDC), on radial maze performance and brain contents of histamine and amino acids in rats. By daily subcutaneous (s.c.) administration of FMH (100 mg kg ), rats showed significant enhancement of a radial maze performance without changes in locomotion. Six days after FMH treatment, the histamine levels both in the cerebral cortex and diencephalon decreased significantly. However, the glutamate and glycine levels significantly increased in the cerebral cortex and hippocampus. These results suggest that FMH enhances the acquisition phase of radial maze study with the increases in glutamate and glycine levels in the cerebral cortex and hippocampus of rats.

Interleukin-6 affects scopolamine-induced amnesia, but not brain amino acid levels in mice.

We have previously shown that, after peripheral administration, different cytokines affect cognitive functions in mice. In this study, we evaluated the effects of mouse interleukin-6 (IL-6) on the classical behavioural test of scopolamine-induced amnesia for a passive avoidance response in the mouse. Pretraining i.p. administration of this cytokine (0.125 and 0.5 microgram/mouse) significantly reduced the amnesic action of the muscarinic receptor antagonist. As it is well known that brain amino acids are deeply involved in the modulation of cognitive processes we measured the levels of glutamine, aspartic acid, glutamic acid and GABA in the hippocampus and hypothalamus of mice treated with IL-6. At both doses which affected the cognitive functions, this cytokine had no effect on brain levels of measured amino acids. Neither nociceptive thresholds to a thermal stimulus, nor spontaneous locomotor activity were modified by the acute administration of IL-6 (0.5 microgram/mouse). Our data confirm previous observations indicating that peripheral administration of cytokines affects some, but not other brain functions and suggest the involvement of IL-6 in the central modifications induced by the immune activation.

Amino Acid Levelsin the Brain of Rats with Peripheral Nerve Constriction or Section

BACKGROUND: Both excitatory and inhibitory amino acids modulate central neuronal activity following peripheral nerve tissue injury.OBJECTIVE: To establish whether mononeuropathy induced by chronic constriction injury or by sectioning of the sciatic nerve affects neurotransmitter amino acid levels in the rat brain areas.METHODS: Glutamine, glutamic acid, gamma‐aminobutyric acid (GABA) and aspartic acid in the hindbrain, midbrain and hypothalamus of rats were measured by high performance liquid chromatography 14 days after surgery.RESULTS: After monolateral nerve ligation an increase in glutamine and a decrease in GABA levels in all brain areas were observed, with no side preference. The section of the sciatic nerve did not cause any modification in amino acid levels.CONCLUSIONS: The results allow one to differentiate more clearly classic models of mononeuropathy from a biochemical point of view. Moreover, results indicate that continuous neuronal stimulation induced by nerve constriction is able to modify some amino acid pathways at a supraspinal level.

Long-term depletion of brain histamine induced by α-fluoromethylhistidine increases feeding-associated locomotor activity in mice with a modulation of brain amino acid levels

We examined the long-term effects of administration of ( S)-α-fluoromethylhistidine (FMH), a specific inhibitor of histidine decarboxylase, on the spontaneous locomotor activity, food intake and brain contents of histamine, catecholamines, serotonin and amino acids of ICR mice. The distance of ambulation and number of rearings significantly increased from 8 to 15 h (20.00-03.00 h) after treatment with FMH (100 mg/kg, i.p.) and the 24-h food intake also increased significantly. On FMH treatment, the locomotor activity in movements of 3–15 cm/0.5 s was greater than that of control mice, whereas the number of slight movements (0–1 cm/0.5 s) decreased, suggesting that once a mouse treated with FMH is in motion, it moves a longer distance than a control mouse. We sacrificed mice 12 or 24 h after FMH treatment to measure the brain contents of histamine, monoamines and amino acids. Decrease of the brain histamine content to 35% of the control level was observed until 24 h after FMH treatment, but no significant changes in the brain catecholamine and serotonin contents were detected. However, the brain GABA content of ICR mice decreased to 85% of control 12 h after FMH treatment. Moreover, decrease of the brain GABA content after FMH treatment was greater in mast cell-deficient W W v mice, being 70 and 62% of the control level 12 and 24 h after treatment, respectively. The present experiments support the idea that the locomotor activity is affected by the central histaminergic system, directly and/or indirectly.

Selective Alterations of Extracellular Brain Amino Acids in Relation to Function in Experimental Portal‐Systemic Encephalopathy: Results of an In Vivo Microdialysis Study

Portal-systemic encephalopathy (PSE) is characterized by neuropsychiatric symptoms progressing through stupor and coma. Previous studies in human autopsy tissue and in experimental animal models of PSE suggest that alterations in levels of brain amino acids may play a role in the pathogenesis of PSE. To assess this possibility, levels of amino acids were measured using in vivo cerebral microdialysis in frontal cortex of portacaval-shunted rats administered ammonium acetate (3.85 mmol/kg, i.p.) to precipitate severe PSE. Sham-operated rats served as controls. Portacaval shunting resulted in significant increases of levels of extracellular glutamine (threefold, p < 0.001), alanine (38%, p < 0.01), aspartate (44%, p < 0.05), phenylalanine (170%, p < 0.001), tyrosine (140%, p < 0.001), tryptophan (63%, p < 0.001), leucine (75%, p < 0.001), and serine (60%, p < 0.001). Administration of ammonium acetate to sham-operated animals led to a significant increase in extracellular glutamine and taurine content, but this response was absent in shunted rats. The lack of taurine release into extracellular fluid following ammonium acetate administration in portacaval-shunted rats could relate to the phenomenon of brain edema in these animals. Ammonium acetate administration resulted in significant increases in the extracellular concentrations of phenylalanine and tyrosine in both sham-operated and portacaval-shunted rats. Severe PSE was not accompanied by significant increases in extracellular fluid concentrations of glutamate, aspartate, GABA, tryptophan, leucine, or serine, suggesting that increased spontaneous release of these amino acids in cerebral cortex is not implicated in the pathogenesis of hepatic coma.

Effect of food deprivation on glutathione and amino acid levels in brain and liver of young and aged rats

The effect of short-term food deprivation on glutathione (GSH) and amino acid levels in brain regions of young and aged rats was compared with changes observed in liver. Animals aged 3 months and 24 months were deprived of food for 48 h. GSH and amino acid levels from cerebral cortex, cerebellum, pons medulla, and liver were assayed and compared with levels in animals of the same age fed normal diets. In liver in both young and old rats, GSH levels fell 30%, from 13 μmol/g tissue to 8/7 μmol/g tissue. Significant changes were observed in other amino acids, including an increase of 30–50% in methionine, glycine, and glutamine, and a decrease of 30–50% in alanine in liver of both young and aged rats, and a 4-fold increase in taurine in young. In brain, little change was observed upon food deprivation. No decrease was observed in GSH, and only small changes were observed in other amino acids. In the aged animal aspartate, glutamate, and alanine levels were slightly lower; tyrosine in cerebellum was reduced by 30%, and both glycine and tyrosine in the pons medulla were reduced by 20–30%. In the brain areas examined, levels of GSH ranged from 1–2 μmol/g in young and 0.8–1.4 μmol/g in old; with levels in pons medulla being lower than those in cerebral cortex. In brain, in contrast to liver, levels were scarcely affected by short-term food deprivation. The relative stability of amino acids paralleled that of brain proteins, which did not significantly decrease even under conditions in which protein content of most other tissues was greatly reduced, indicating specific control of cerebral protein metabolism in protection in malnutrition.

Brain amino acid levels are related to seizure propensity in the gerbil ( Meriones unguiculatus)

1. 1. Gerbils were scored for seizure severity and duration and ambulatory and rearing behaviours on presentation with an “open field”. 2. 2. Eight seizure-prone (SP) and eight non-seizure-prone (NSP) gerbils were killed and their brains treated to inactivate enzymes before division into corticate and decorticate regions for amino acid analysis. 3. 3. SP animals showed more ambulatory activity on later presentations (trials 3–5) with the open field compared to NSP animals. 4. 4. Statistics showed seizure propensity related to high levels of glutamine and arginine and to low levels of glutamate, aspartate, citrulline, cysteine and glycine. 5. 5. These results suggest aspects of glucose and/or amino acid metabolism may be responsible for behavioural differences in SP compared to NSP gerbils.

Changes in the brain levels of GABA and related amino acids in anoxic shore crab (Carcinus maenas).

The effects of anoxia on the brain concentrations of gamma-aminobutyric acid (GABA), glutamate, aspartate, glutamine, alanine, and taurine were measured in the shore crab (Carcinus maenas) and compared with data previously obtained from anoxia-tolerant vertebrates. C. maenas was found to survive 12 h in nitrogen-bubbled water. The changes found in brain amino acid levels were strikingly similar to those seen in anoxia-tolerant vertebrates. Thus, during anoxia, the brain of C. maenas displayed considerable increases in the concentrations of GABA (2.4-fold increase after 12 h) and alanine (8-fold increase after 12 h). By contrast, the brain levels of glutamate, aspartate, and glutamine fell significantly during anoxia, whereas the taurine level remained unchanged. Because GABA is a major inhibitory neurotransmitter in arthropods (as well as in most animal phyla), it is suggested that the increased level of GABA could promote the anoxic metabolic depression displayed by C. maenas and thus prolong anoxic survival. It is also possible that the decreases in glutamate and aspartate levels could play similar roles.

β-Adrenergic regulation of amine precursor amino acid transport across the blood-brain barrier

β-Adrenoceptor agonists were administered i.p. into rats and amino acid levels in brain and plasma were then determined to assess the effects on transport across the blood-brain barrier. Isoproterenol (10 μmol/kg) caused significant increases in aromatic amino acid (tyrosine, phenylalanine and tryptophan) levels in cerebral cortex and decreases in almost all amino acid concentrations in plasma. This effect of isoproterenol on brain tyrosine level was dose-dependent with an ED 50 of 0.25 μmol/kg. Salbutamol ( β 2-adrenoceptor agonist, 10 μmol/kg) showed similar effects, but dobutamine ( β 1-adrenoceptor agonist, 50 μmol/kg) failed to increase brain amino acid levels. When l-threo-3,4-dihydroxyphenylalanine (L-DOPA, 100 μmol/kg) was i.p. loaded, β-adrenoceptor agonists promoted the transport of L-DOPA into brain without increasing the clearance rate of plasma L-DOPA. Moreover, significant increases in dopamine and its metabolites were observed in rat brain. These findings suggest that the transport of aromatic amino acids across the blood-brain barrier may be regulated through β 2-adrenoceptors and that co-administration of β 2-adrenoceptoragonists with L-DOPA may enhance the therapeutic efficacy of L-DOPA.

Effect of acetyl‐L‐carnitine on the dopaminergic system in aging brain

We studied the effect of acetyl-L-carnitine (ALCAR) on dopamine release and the effect of long-term acetyl-L-carnitine treatment on age-related changes in striatal dopamine receptors and brain amino acid levels. In striatal tissue that had been incubated with [3H]dopamine, acetyl-L-carnitine increased the release of [3H]dopamine evoked by electrical stimulation. In striatal tissue from aged mice administered acetyl-L-carnitine for 3 months, the release of [3H]dopamine evoked by electrical stimulation was higher than that of its aged control; the release after a second stimulation was similar in the two groups. There was a significant decline in the number of D1 striatal dopamine receptors with age. The Bmax was 51% lower in 1.5-year-old mice than in 4-month-old animals. Administration of acetyl-L-carnitine for 3 months diminished the reduction in the binding of [3H]SCH-23390. [3H]Spiperone binding to D2 receptors was not decreased with age and was not affected by acetyl-L-carnitine treatment. Age-related decreases in levels of several amino acids were observed in several brain regions. Acetyl-L-carnitine lessened the reduction in the level of taurine only in the striatum. The findings confirm the multiple effects of acetyl-L-carnitine in brain, and suggest that its administration can have a positive effect on age-related changes in the dopaminergic system.