Comparative analysis of ribonuclease P RNA structure in Archaea

The relationship between central serotonergic activities and voluntary alcohol consumption was studied in Sprague-Dawley rats, which normally have low alcohol preference. After initial screening for an evenly matched baseline alcohol preference, selective central serotonergic lesioning was induced by intracisternal injection of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). Control rats received injections of vehicle only. Both 5,7-DHT and vehicle-treated rats were further divided into two subgroups, which either had continued free access to ethanol (alcohol-drinking) or were deprived of it (alcohol-free). All rats were then tested again for alcohol preference. All rats were then killed, and the levels of monoamines in the brains were determined by high performance liquid chromatography with electrochemical detection. Behavioral results indicated that all 5,7-DHT-treated rats had significantly higher alcohol preference and consumption than the corresponding sham controls. Except in the cerebellum, the 5,7-DHT-treated rats had significantly lower levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in most brain regions compared with those in the corresponding sham controls. Treatment with 5,7-DHT also resulted in a decrease in serotonin turnover in all brain regions in the alcohol-free rats, except in the cerebellum. In alcohol-drinking rats, however, 5,7-DHT treatment only reduced serotonin turnover in the pons. The levels of norepinephrine and dopamine in several brain regions were not significantly different. Thus, it appeared that in the Sprague Dawley rats, 5,7-DHT treatment depleted 5-HT and 5-HIAA levels in most brain regions while increasing alcohol consumption. Chronic alcohol-drinking attenuated the increase in alcohol consumption associated with serotonergic lesions. Voluntary alcohol consumption seemed more associated with 5-HT turnover than with tissue 5-HT levels. Our data also suggested that tolerance to alcohol-induced hypothermia was primarily attributable to long-term alcohol drinking rather than serotonergic lesioning.     

Intranigral or intrastriatal injections of GDNF: effects on monoamine levels and behavior in rats

The present studies were designed to determine whether administration of recombinant human glial cell line-derived neurotrophic factor (rhGDNF) into either the substantia nigra or striatum is capable of augmenting dopamine function of the nigrostriatal pathway in normal rats. Single bolus intracranial injections of rhGDNF at either site increased locomotor activity and decreased food and water consumption and body weight in a dose-dependent manner when compared to vehicle-treated animals. These behavioral responses returned to pre-control levels within 3 weeks post rhGDNF administration. Administration of rhGDNF intranigrally increased dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels of the ipsilateral substantia nigra at 2 and 6 weeks post injection but had no augmenting effects on dopamine or its metabolites in the striatum. Administration of rhGDNF intrastriatally increased DOPAC and HVA levels of the ipsilateral striatum, although striatal dopamine levels were unchanged. Ipsilateral nigral dopamine levels were increased after intrastriatal injection of rhGDNF. The effects of intracranial rhGDNF were not specific to the nigrostriatal dopamine system, since nigrostriatal serotonin, 5-hydroxyindoleacetic acid (5-HIAA), epinephrine and norepinephrine transmitter levels were altered depending on administration route for rhGDNF and dose. Taken together, these data demonstrate long-lasting neurochemical and behavioral changes which suggest that rhGDNF can augment function in adult rat dopamine neurons. Therefore, rhGDNF may have therapeutic potential for Parkinson's disease.     

Neurochemical variables in schizophrenic patients during switching from neuroleptics to clozapine

1. The study aimed to search for the effect of clozapine on the levels of the main metabolites of dopamine homovanillic acid (HVA), serotonin 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine 3-methoxy-4-hydroxyphenylglycol (MHPG) in urine as well as on plasma levels of HVA, 5-HIAA, prolactin (PRL) and cortisol. 2. Seventeen male patients diagnosed as suffering from DSM-IIIR schizophrenia completed the study. 3. The patients were switched from classical antipsychotics to clozapine. After six weeks treatment with clozapine the severity of psychopathology (total BPRS score) decreased significantly (p = 0.00004). pHVA and -5-HIAA did not change significantly. uMHPG increased significantly (p = 0.017). Both PRL and cortisol levels decreased significantly (p = 0.0002, p = 0.032 respectively). Patients with high HVA levels in both plasma and urine at baseline had a lower BPRS score at the end of treatment period (p = 0.0001, p = 0.049 respectively).     

Alcohol exposure during development alters hypothalamic neurotransmitter concentrations

The effect of exposure to alcohol during a period roughly equivalent to the human third trimester on neurotransmitter content in the rat hypothalamus was examined. The alcohol exposure was accomplished via an artificial rearing procedure. The alcohol group was exposed to 5 g/kg/day of ethanol from postnatal day (PD) 4 to 10. There was an artificially reared control group not exposed to alcohol and a normally reared control group. Noradrenaline, dopamine, homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin, and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were measured using high performance liquid chromatography with electrochemical detection in juvenile and adult rats. There were no effects in juvenile rats. In adult rats, alcohol exposure from PD 4 to 10 increased hypothalamic content of noradrenaline, dopamine, serotonin and 5-HIAA. While adult females had greater amounts of hypothalamic serotonin and 5-HIAA than adult males, there were no interactions of sex with alcohol exposure. These results suggest that hypothalamic function is seriously disrupted by alcohol exposure during development.     

Cerebral ventricle-brain ratio in monozygotic twins discordant and concordant for schizophrenia

The influence of tetrapeptide tuftsin (Tyr-Lys-Pro-Arg) on learning, exploratory activity, emotional behavior, and hypothalamic monoamine content was studied in Wistar rats with different resistance to stress induced by acoustic stimuli. Positive effects of taftsin were more pronounced in low-resistant rats. Administration of taftsin induced in these animals a significant increase in reactivity to stimuli of different modalities, the open-field exploratory activity, rate of alimentary conditioning and its modification in emotionally negative situation. Biochemical examinations showed that in rats with high resistance to stress taftsin administration led to a decrease in hypothalamic noradrenaline level and increase in dopamine and serotonin levels. On the contrary, in low-resistant animals taftsin increased the level of noradrenaline and decreased that of dopamine, serotonin, and 5-hydroxyindoleacetic acid. It is suggested that different behavioral effects of taftsin in stress-resistant and nonresistant rats are caused by its different influence on hypothalamic biogenic amines.     

The function of Glu338 in the catalytic triad of the carbamoyl phosphate synthetase amidotransferase domain

The purpose of the present study was to investigate whether differences in the function of monoaminergic systems could account for the variability in attention and impulsive behaviour between rats tested in the five-choice serial reaction time task in a model of attention deficit hyperactivity disorder. The ability of a rat to sustain its attention in this task can be assessed by measuring choice accuracy (percent correct responses) to visual stimuli, whereas the percentage of premature responses indicates the level of impulsivity. Following training with the five-choice serial reaction time task, rats were decapitated and brain pieces taken for neurochemical determination. Levels of dopamine, noradrenaline, 5-hydroxytryptamine, the dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid and the 5-hydroxytryptamine metabolite, 5-hydroxyindoleacetic acid were determined in the frontal cortex, nucleus accumbens, dorsal striatum and hippocampus. Multivariate regression analysis with a stepwise method revealed that the indeces of utilization of serotonin (5-hydroxyindoleacetic acid/5-hydroxytryptamine) in the left frontal cortex and dopamine (3,4-dihydroxyphenylacetic acid/dopamine) in the right frontal cortex together accounted for 49% of the variability in attentional performance between subjects. According to the regression analysis, a negative correlation existed between the left frontal cortex 5-hydroxyindoleacetic acid/5-hydroxytryptamine and choice accuracy, and a positive correlation was observed between 3,4-dihydroxyphenylacetic acid/dopamine ratio and choice accuracy on the opposite hemisphere. Additionally, right frontal cortex serotonin utilization was found to correlate positively with the proportion of premature hole responses and this relation accounted for about 24% of the variability in this index of impulsivity between animals. These data indicate that frontal cortex dopamine and serotonin play an important role in the modulation of attention and response control.     

Distinct activation of monoaminergic pathways in chick brain in relation to auditory imprinting and stressful situations: a microdialysis study

In the forebrain of the domestic chick (Gallus gallus domesticus), an area termed the mediorostral neostriatum/hyperstriatum ventrale is strongly involved in emotional learning paradigms such as acoustic filial imprinting. Furthermore, the involvement of the mediorostral neostriatum/hyperstriatum ventrale in stressful situations, such as social separation, has been demonstrated in 2-deoxyglucose studies. The aim of the present study was to examine whether quantitative changes of dopamine, serotonin and their metabolites occur during auditory filial imprinting and during social separation. Using in vivo microdialysis in tone-imprinted and in naive, control chicks, we compared the extracellular levels of homovanillic acid, a metabolite of dopamine, and 5-hydroxyindoleacetic acid, a metabolite of serotonin, during the presentation of the imprinting tone. A small, but statistically significant, decrease of extracellular homovanillic acid levels was found in the mediorostral neostriatum/hyperstriatum ventrale of imprinted chicks compared to control animals, whereas changes of 5-hydroxyindoleacetic acid were not detected. In a second experiment, we investigated the levels of homovanillic acid and 5-hydroxyindoleacetic acid in the mediorostral neostriatum/hyperstriatum ventrale of socially reared chicks during different stress situations, such as handling or separation from their cage mates. Handling induced a significant increase of homovanillic acid and 5-hydroxyindoleacetic acid, while social separation resulted in a significant increase of 5-hydroxyindoleacetic acid and only a slight increase of homovanillic acid. Despite considerable inter-individual variability, the increase of distress vocalizations (duration of distress calls) after social separation displayed a good correlation to the increased 5-hydroxyindoleacetic acid levels in all animals analysed. These results provide the first evidence that the physiological response of the mediorostral neostriatum/hyperstriatum ventrale related to different emotional conditions after acoustic imprinting and during stressful situations is, at least in part, mediated by dopaminergic and/or serotonergic pathways. Furthermore, the results from the present study indicate a distinct activation of dopaminergic and serotonergic pathways in relation to the behavioural situation and the associated changes of emotional status.     

Influence of neonatal and adult hyperthyroidism on behavior and biosynthetic capacity for norepinephrine, dopamine and 5-hydroxytryptamine in rat brain

In neonatal rats, administration of l-triiodothyronine (10 mug/100 g/day) for 30 days presented signs of hyperthyroidism which included accelerated development of a variety of physical and behavioral characteristics accompanying maturation. The spontaneous motor activity was increased by 69%. Exposure of developing rats to thyroid hormone significantly increased the endogenous concentration of striatal tyrosine and the activity of tyrosine hydroxylase as well as the levels of dopamine in several brain regions. The concentration of striatal homovanillic acid and 3,4-dihydroxyphenylacetic acid, the chief metabolites of dopamine, was also increased and the magnitude of change was greater than the rise in dopamine. Despite increases in the activity of tyrosine hydroxylase and the availability of the substrate tyrosine, the steady-state levels of norepinephrine remained unaltered in various regions of brain except in cerebellum. Futhermore, neonatal hyperthyroidism significantly increased the levels of midbrain tryptophan and tryptophan hydroxylase activity but produced no change in 5-hydroxytryptamine levels of several discrete brain regions, except hypothalamus and cerebellum where its concentration was slightly decreased. However, the 5-hydroxyindoleacetic acid levels were enhanced in hypothalamus, ponsmedulla, midbrain, striatum and hippocampus. The elevated levels of 5-hydroxyindoleacetic acid did not seem to be due to increased intraneuronal deamination of 5-hydroxytryptamine since monoamine oxidase activity was not affected in cerebral cortex and midbrain of hyperthyroid rats. The data demonstrate that hyperthyroidism significantly increased the synthesis as well as the utilization of catecholamines and 5-hydroxytryptamine in maturing brain. Since the mature brain is known to respond differently to thyroid hormone action than does the developing brain, the effect of L-triiodothyronine treatment on various putative neurohumors also was examined in adult rats. Whereas administration of l-triiodothyronine (10 mug/100 g/day) for 30 days to 120-day-old rats increased the levels of tyrosine by 23% and of tryptophan by 43%, no appreciable change was noted in tryptophan hydroxylase activity. In contrast to neonatal hyperthyroidism, excess of thyroid hormone in adult rats failed to produce any change in motor activity and tended to decrease striatal tyrosine hydroxylase activity only slightly. The concentration of dopamine remained unchanged in all regions of the brain except in midbrain where it rose by 19%. Whereas norepinephrine concentration was altered in hypothalamus, pons-medulla and midbrain, the levels of 5-hydroxytryptamine and its metabolite, 5-hydroxyindoleacetic acid, were significantly decreased in striatum and cerebellum. Since dopaminergic and noradrenergic neurons are the critical components of the motor system, the possibility exists that elevated behavioral activity in young L-triiodothyronine-treated animals might be associated with increased turnover of catecholamines in neuronal tissue.     

Naloxone-precipitated changes in biogenic amines and their metabolites in various brain regions of butorphanol-dependent rats

Influence of a naloxone (an opioid receptor antagonist) challenge (5 mg/kg, IP) on levels of biogenic amines and their metabolites in various brain regions of rats infused continuously with butorphanol (a mu/delta/kappa mixed opioid receptor agonist; 26 nmol/microliter/h) or morphine (a mu-opioid receptor agonist; 26 nmol/microliter/h) was investigated using high-performance liquid chromatography with electrochemical detection (HPLC-ED). Naloxone precipitated a withdrawal syndrome and decreased the levels of: dopamine (DA) in the cortex and striatum, 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum, homovanilic acid (HVA) in the striatum, limbic, midbrain, and pons/medulla regions in butorphanol-dependent rats. However, the levels of norepinephrine (NE), serotonin (5-hydroxytryptamine; 5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the regions studied were not affected by naloxone-precipitated withdrawal. In addition, naloxone increased the HVA/DA ratio in the cortex, while this ratio was reduced in the limbic, midbrain, and pons/medulla. The reduction of 5-HIAA/5-HT ratio was also detected in the limbic area. In the animals rendered dependent on morphine, the results obtained were similar to those of butorphanol-dependent rats except for changes of 5-HIAA levels in some brain regions. These results suggest that an alteration of dopaminergic neuron activity following a reduction of DA and its metabolites in specific brain regions (e.g., striatum, limbic, midbrain, and pons/medulla) play an important role in the expression of the opioid withdrawal syndrome.     

Efficacy of taxol in the orpk mouse model of polycystic kidney disease

Studies on conscious Sprague-Dawley rats using intracerebral dialysis in live animals combined with high-performance liquid chromatography with electrochemical detection showed that administration of apomorphine into the nucleus accumbens decreased the levels of dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid in the extracellular space of the dorsal striatum throughout the observation period and produced a transient reduction in the level of homovanillic acid in the dialysate from this structure. The studies demonstrated that reversible exclusion of the nucleus accumbens with procaine produced a transient increase in the levels of dopamine metabolites, without an increase in serotonin metabolites, in the extracellular space of the dorsal striatum. These results demonstrate that the nucleus accumbens affects dopamine metabolism in the striatum, this being mediated by the dopamine-reactive system in the nucleus accumbens.     

Dexamethasone changes brain monoamine metabolism and aggravates ischemic neuronal damage in rats

BACKGROUND: Glucocorticoids have been reported to aggravate ischemic brain damage. Because changes in the activities of various neuronal systems are closely related to the outcome of ischemic damage, the authors evaluated the effects of dexamethasone on the monoaminergic systems and ischemic neuronal damage. METHODS: The right middle cerebral artery was occluded for 2 h, and the tissue concentrations of monoamines and their metabolites were determined in the cerebral cortex and the striatum of rats. The turnover of 5-hydroxytryptamine was compared in animals injected with saline and those injected with dexamethasone twice (2 mg/kg in each injection) by evaluating the probenecid-induced accumulation of 5-hydroxyindoleacetic acid. The turnovers of norepinephrine and dopamine were estimated from the alpha-methyl-p-tyrosine-induced depletion of norepinephrine and dopamine, respectively. The effect of dexamethasone on the infarct volume was evaluated by triphenyltetrazolium chloride stain in rats subjected to 2 h of occlusion. RESULTS: Dexamethasone did not affect the cortical 5-hydroxytryptamine or 5-hydroxyindoleacetic acid contents. However, it suppressed the turnover of the cortical 5-hydroxytryptamine on both sides. Dexamethasone reduced the turnover of the striatal 5-hydroxytryptamine and facilitated the dopamine turnover. In rats subjected to 2 h of occlusion and 2 h of reperfusion, the infarct volume was 10.5 times greater in the group that received dexamethasone than in the animals that received saline. CONCLUSIONS: Dexamethasone suppresses the inhibitory serotonergic system and facilitates the excitatory dopaminergic system in the rat telencephalon. This may be a mechanism by which dexamethasone aggravates ischemic neuronal injury.     

Coupled-column liquid chromatographic analysis of catecholamines, serotonin, and metabolites in human urine

A column-switching HPLC system was utilized for the simultaneous determination of epinephrine, norepinephrine, dopamine, serotonin, and their metabolites metanephrine, normetanephrine, 3, 4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid in human urine. The sample was injected directly onto a C18-alkyl-diol silica precolumn, which separated the analytes from matrix. The analytes were eluted from the precolumn onto the analytical column by the use of column-switching techniques and were then separated on the analytical column by means of ion-pair reversed-phase HPLC. The analytes were then oxidized to the corresponding quinones and converted into fluorescent derivatives by reaction with meso-1,2-diphenylethylenediamine.     

Medicine in the vocal arts

The effects of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) on the central nervous system (CNS) were studied in rats. Behavioural and neurochemical studies were performed. Results show that acute and oral administration of dimethylamine 2,4-D was able to decrease locomotion and rearing frequencies and to increase immobility duration of rats observed in an open-field test. Treatment of rats with p-chlorophenylalanine (PCPA) was unable to change rat's open-field behaviour; 5-hydroxytryptophan (5-HTP) administration not only increased locomotion and rearing frequencies but also decreased immobility duration. Pretreatment of the rats with PCPA and 5-HTP decreased and increased dimethylamine 2,4-D effects, respectively. The herbicide was not able to change the striatal levels of dopamine and homovanilic acid but decreased the striatal levels of serotonin (5-HT), as observed for the doses of 100 and 200 mg/kg and increased those of 5-hydroxyindoleacetic acid (5-HIAA) as measured after the 200 mg/kg dose treatment. When the levels of serotonin and 5-HIAA were measured at the brain stem level, only those of 5-HIAA were modified, being increased by diethylamine 2,4-D (60; 100 and 200 mg/kg); this increment on 5-HIAA levels was observed even 1 hr after pesticide administration. Further analysis showed that 2,4-D concentrations chromatographically detected both in serum and brain of the intoxicated animals were dose-dependent, being found as early as 1 hr after the smaller dose of the herbicide used (10 mg/kg). The results suggest that diethylamine 2,4-D modify 5-HT functional activity within the CNS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Central monoamines and hyperkinase of childhood

Lumbar cerebrospinal fluid levels of homovanillic acid and 5-hydroxyindoleacetic acid, the major metabolites of dopamine and serotonin, respectively, in hyperactive children did not differ significantly from those of age-matched controls. Dextroamphetamine treatment substantially reduced the spinal fluid content of homovanillic acid but not of 5-hydroxyindoleacetic acid. No change in levels of either monoamine metabolite occurred with placebo therapy. In hyperactive children receiving dextroamphetamine, the amount of homovanillic acid decline correlated closely with the degree of clinical improvement. These results support the view that an alteration in central dopamine-mediated synaptic function may occur in children manifesting the hyperactive syndrome.     

Regional and temporal separation of serotonergic activity mediating social stress

Stressful aggressive interaction stimulates central serotonergic activation in telencephalon as well as brainstem. Social roles can be distinguished by monoamine activity following aggression. Pairs of male lizards, Anolis carolinensis, were allowed to fight and form dominant/subordinate relationships. In micropunched regions of telencephalon, the greatest serotonergic changes occur in subordinate males. In hippocampal cortex and nucleus accumbens, subordinate males have increased 5-hydroxyindoleacetic acid/serotonin at 1 h following the fight. In these areas the ratio gradually decreases over a week of cohabitation, as was previously reported for brainstem. Medial and lateral amygdala develop increased serotonergic activity more slowly, with the greatest increase being evident following a week of interaction. Turnover, serotonin and 5-hydroxyindoleacetic acid levels in amygdala escalate over the first week of interaction in subordinate males, and return to baseline by one month. In dominant males, the pattern is accelerated, with the most extensive serotonin system activity present at 1 h, then decreasing over a month. The patterns of serotonergic activation are so similar in hippocampus, nucleus accumbens and brainstem that a co-ordinated response may be involved in mediating short-term social stress and aggression. Similarly, medial and lateral amygdala exhibit corresponding, but delayed patterns in subordinate males, suggesting a co-ordinated response in these regions mediating longer-term stress responses. These data are consistent with rapid neuroendocrine stress modulation in dominant individuals, and delayed serotonergic activity changes in subordinate males.     

Association between low contents of dopamine and serotonin in the nucleus accumbens and high alcohol preference

The contents of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were determined in the nucleus accumbens (ACB), frontal cortex (FR), anterior striatum (AST), and hippocampus (HIP) of adult male rats from the F2 generation of P x NP intercrosses. Rats were tested for their alcohol preference and were divided into two groups, depending on their alcohol intake. Rats in the high drinking group (n = 11) had ethanol intakes > 5g/kg/day, whereas the low drinking group (n = 15) had values < 1 g/kg/day. The content of DA in the ACB was lower (p < 0.001) in the high alcohol drinking group (46 +/- 2 pmol/mg tissue) than in the low intake rats (61 +/- 3 pmol/mg tissue). However, the contents of DOPAC and HVA in the ACB were similar for both groups. There were no differences between the two groups in the contents of DA in the FR or AST. The content of 5-HT in the ACB was lower (p < 0.05) in high alcohol drinking rats (6.3 +/- 0.3 pmol/mg tissue) than in the low intake group (7.0 +/- 0.2 pmol/mg tissue). The content of 5-HIAA in the ACB of the high intake rats was also lower than the level for the low drinking rats. There were no differences in the contents of 5-HT or 5-HIAA in the FR, HIP, and AST between the two groups. The results confirm a phenotypic association between abnormal DA and 5-HT systems projecting to the ACB and high alcohol drinking behavior in the P line of rats.     

Monoamine activity in anterior hypothalamus of guinea pig pups separated from their mothers.

Brief isolation in a novel environment increased the ratios of 3-methoxy-4-hydroxyphenylethylene glycol to norepinephrine (MHPG:NE) and dihydroxyphenylacetic acid to dopamine (DOPAC:DA) in the anterior hypothalamus of 44 guinea pig pups. Ratios were significantly elevated after 90 min of isolation and for MHPG:NE, after 30 min of isolation; changes were due to increases in MHPG and DOPAC. Home cage isolation produced no change in any measure of catecholamine activity. No changes in levels of serotonin or its metabolite were observed. In Exp 1, resting levels of NE and DOPAC:DA were predictive of the rate of separation-induced vocalization. Maternal separation in the context of novelty increases hypothalamic NE and DA activity; however, both isolation and novelty are required because neither maternal separation in the home cage nor exposure to a novel cage together with the mother had any discernible effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Identification and characterization of CDS2, a mammalian homolog of the Drosophila CDP-diacylglycerol synthase gene

The technique of intracranial microdialysis was used to investigate the effects of aging on the striatal dopaminergic system of the anesthetized Fischer 344 rat. Microdialysis probes were implanted into the striatum of young (2-8 months) and aged (24-28 months) urethane anesthetized rats. Striatal dialysate levels were analyzed for dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and serotonin (5-HT) by high performance liquid chromatography with electrochemical detection. As compared to the young animals, basal extracellular levels of DA and DOPAC were significantly decreased in two groups of aged animals. Stimulation with excess potassium added through the microdialysis probe produced a robust overflow of DA in the young and aged rat striatum, but the evoked overflow of DA was not diminished in the aged rat striatum as compared to young animals. In contrast, d-amphetamine-evoked overflow of DA was again robust in young and aged animals, but was greatly decreased in the aged rat striatum as compared to the signals recorded in the young rats. Taken together with previous reports, these data support the hypothesis that a major change in the regulation of DA release that occurs in aging involves changes in the function of the neuronal uptake of DA, which may be a compensatory property of DA neurons in senescence.     

Higher plants light harvesting proteins. Structure and function as revealed by mutation analysis of either protein or chromophore moieties

In vivo microdialysis was used to examine the effects of dopaminergic transplants on extracellular concentrations of dopamine (DA), serotonin (5-HT), and their precursors and major metabolites in the denervated rat striatum. Dialysis perfusates were collected from intact 6-hydroxydopamine (6-OHDA) lesion plus sham grafted, and lesion plus fetal substantia nigra (SN) grafted striata. The SN transplants ameliorated the reduction of striatal DA and dihydroxyphenylacetic acid (DOPAC) levels in rats with unilateral 6-OHDA lesions of the mesostriatal pathway. The transplants also increased extracellular levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the denervated striatum. In response to NSD-1015 (an inhibitor of aromatic L-amino acid decarboxylase, AADC), 5-hydroxytryptophan (5-HTP) levels were substantially elevated in the SN grafted striata as compared with those in the sham grafted controls, which continued even after subsequent administration of L-3,4-dihydroxyphenylalanine (L-DOPA, 100 mg/kg i.p.). Immunohistochemical analysis showed hyperinnervation of 5-HT fibers in the grafted striatum, which was consistent with the results of microdialysis experiments. These results indicated that implantation of SN grafts into the 6-OHDA-lesioned striatum of rats induces hyperactivity of 5-HT synthesis, release and metabolism.     

Effects of food restriction on the periodicity of corticosteroids in plasma and on monoamine concentrations in discrete brain nuclei

The concentrations of plasma corticosteroids and of norepinephrine, dopamine and serotonin in microdissected brain regions were measured at 08.00, 12.00 and 20.00 h in male rats fed ad libitum and in rats whose food intake was restricted to 09.30-11.30 h. In ad libitum fed animals, plasma corticosteroids were lowest at 08.00 and highest at 20.00 h. As demonstrated previously, restriction of food availability was associated with appearance of a peak in corticosteroids at 08.00 h. In ad libitum fed animals, serotonin and dopamine concentrations in the median eminence were higher at 20.00 than at 08.00 h. Restriction of food availability significantly decreased the levels of these neurotransmitters at 20.00 h. In the paraventricular nucleus, amygdala, and hippocampus of ad libitum fed animals, serotonin levels were lower at 20.00 than at 08.00 or 12.00 h. In food-shifted animals, this pattern was reversed so that lowest levels of serotonin occured at 08.00 and markedly elevated levels were observed at 12.00 and 20.00 h. No changes were noted in norepinephrine content of the median eminence or paraventricular nucleus of ad libitum fed or food restricted animals. These results indicate that the shift in the periodicity of corticosteroid secretion produced by a restricted feeding regime is accompanied by changes in the periodicity of neurotransmitter concentrations in specific regions of the brain, and that such patterns are dissimilar in different regions.