Dorsal lesions of the prefrontal cortex: effects on alcohol consumption and subcortical monoaminergic systems

Male Wistar rats were subjected to either bilateral aspiration lesions of the dorsal regions of the prefrontal cortex (PFC) or sham lesions and placed on a 6-week, modified sucrose-fading procedure. At the time of sacrifice, the size of the lesion, both in anterior-posterior and medial-lateral dimensions, was measured. Following sacrifice, levels of dopamine (DA), serotonin (5-HT), norepinephrine (NE), and their metabolites were measured in the midbrain (raphe) and nucleus accumbens (NA). Lesioned animals had reductions in 5-HT in the NA, and DA and NE in the raphe. The lesioned group drank more of a solution of 5% alcohol than controls early in the sucrose fading, and less during the later stages. In the lesioned group, the size of the left- and right-hemisphere lesions predicted 5-HIAA levels in the NA, and 5-HT and 5-HIAA levels in the raphe. A laterality effect was noted, such that the size of left-hemisphere lesions were positively associated with raphe 5-HT and 5-HIAA levels, and negatively associated with 5-HT levels in the NA, while right-hemisphere lesions showed the opposite relationships. In addition, the width of the left-hemisphere lesion predicted some measures of alcohol intake. These results suggest that, in the rat, the dorsal PFC is involved in the regulation of monoamines in subcortical regions known to be important in the regulation of reinforced behaviors, and that this regulation differs between hemispheres and shows a laterality effect. In addition, the dorsal PFC appears to have a subtle involvement in the regulation of alcohol intake.     

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.     

Role of tryptophan in the elevated serotonin-turnover in hepatic encephalopathy

The increase of the brain levels of 5-hydroxyindoleacetic acid (5-HIAA) in hepatic encephalopathy (HE) suggests an increased turnover of serotonin (5-HT). To study the role of tryptophan on the increased brain 5-HT metabolism in HE, we attempted to monitor brain levels of tryptophan in rats with thioacetamide-induced acute liver failure by intravenous infusion of branched-chain amino acids (BCAA). The effect of this treatment on 5-HT synthesis and metabolism was investigated in five brain areas. BCAA-infusions (1 and 2 gm/kg/24 h) increased the ratio BCAA/aromatic amino acids in plasma two- and fourfold, respectively, and lowered both plasma and brain levels of tryptophan. At the higher BCAA-dose all parameters suggesting an altered brain 5-HT metabolism (increased brain levels of 5-HT and 5-HIAA, increased 5-HIAA/5-HT ratio) were almost completely normalized. These results provide further evidence for the role of tryptophan in the elevation of brain 5-HT metabolism and for a potential role of BCAA in the treatment of HE.     

Acute effect of 17 beta-estradiol and lithium on ovariectomized rat brain biogenic amines metabolism

The effect of 17 beta-estradiol (E2) on the response of dopamine (DA) and serotonin (5-HT) to acute lithium in the brains of ovariectomized rats was investigated. An E2 injection (100 ng/s.c.) to ovariectomized rats did not change striatal DA levels, whereas the levels of its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), increased 30 min later; concentrations of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), also remained unchanged. In the frontal cortex, DA, 5-HT, HVA and 5-HIAA levels remained unchanged after the E2 injection, whereas DOPAC levels and DOPAC/DA and HVA/DA ratios increased 30 min later. Injection of LiCl (10 mEq) decreased striatal DA levels, increased DOPAC levels and slightly decreased HVA levels; by contrast, frontal cortex DA and HVA levels increased but DOPAC levels were unchanged. A biphasic response of striatal 5-HT levels occurred, increasing shortly after injection of LiCl, followed by a decrease; 5-HIAA levels, however, increased. In the frontal cortex, injection of rats with LiCl led to a gradual increase in 5-HT levels, whereas 5-HIAA concentrations decreased. In the presence of E2, LiCl effected a greater decrease in striatal DA than injection of LiCl alone, advanced the DOPAC peak by 30 min and increased HVA levels; E2 had less effect on the 5-HT response to LiCl, except the decreases in 5-HT and 5-HIAA at 60 min were greater. Furthermore, in the striatum, the increased DA turnover caused by LiCl, estimated by the DOPAC/DA and HVA/DA ratios, was advanced in rats treated with E2. In the presence of E2, LiCl slightly increased frontal cortex DA, DOPAC and HVA levels compared with treatment with LiCl alone, whereas DOPAC levels decreased in rats treated with LiCl + E2 compared with levels in E2-treated rats. Generally, higher levels of 5-HT and 5-HIAA were measured in the frontal cortices of rats treated with LiCl + Ex compared with rats injected with LiCl. These results indicate that E2 potentiates the acute effect of lithium on striatal and frontal cortex DA and 5-HT levels and metabolism, suggesting a role of the hormonal state on this drug response.     

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.     

Changes in dopamine, serotonin and their metabolites in discrete brain areas of rat offspring after in utero exposure to cocaine or related drugs

The concentrations of dopamine (DA), serotonin (5HT) and their metabolites were quantified in 5 brain areas of rats exposed to saline, cocaine (15 mg/kg b.i.d.), amitriptyline (10 mg/kg), or amfonelic acid (AFA, 1.5 mg/kg) throughout gestation. Male pups from 3 similarly treated dams were fostered to 2 surrogate dams. The process of breeding and rearing was repeated 4 times with new dams to build the groups to 4-12, since only one pup per litter was used for any one measurement. AFA was used to mimic the dopamine (DA) uptake blockade and stimulant properties of cocaine and amitriptyline was used to mimic the other pharmacological effects of cocaine. At postnatal days (PND) 30, 60, and 180, one pup per litter was removed for HPLC analysis of monoamines. A second pup received 0.3 mg/kg haloperidol, catalepsy assessed after 1 hr, and the brain used for analysis. The cataleptic response to haloperidol was unaffected by any prenatal treatment. The striatum from PND 30 cocaine rats had decreased levels of DA without a decrease in DA metabolites. At PND 60 in cocaine exposed rats, DA and DOPAC concentrations were increased, and 5HT levels were decreased in the striatum. The amitriptyline-exposed group exhibited decreased 5HT and 5-HIAA levels in the striatum. The hypothalamus of the cocaine group had lower levels of 5-HIAA, and other brain areas had a trend for lower levels of 5HT and 5-HIAA. At PND 180, DOPAC was increased in the striatum and prefrontal cortex of the cocaine group. Haloperidol-induced altered monoamine metabolism was unaffected by any prenatal treatment at any age. These data suggest that age-related changes in the DA and 5HT neurotransmission systems occur in rats exposed prenatally to cocaine. However, the ability of the dopaminergic system to respond to a challenge by a DA receptor blocker is unaltered by these in utero treatments.     

The diagnostic value of hyperostosis in midline subfrontal meningioma

In vivo blockade of 5-HT uptake was studied by investigating the effect of drug pretreatment on the ability of p-chloramphetamine to lower rat brain 5-HT levels. Org 6582 was approximately twice as potent as fluoxetine, five times more potent than chlorimipramine and 14 times more potent than desipramine in blocking the ability of p-chloroamphetamine to lower rat brain 5-HT content. Org 6582 also had a longer duration of action than either fluoxetine or chlorimipramine. Org 6582, whilst having no effect on amine steady state levels, decreased rat brain 5-HT turnover and also lowered rat brain levels of 5-HIAA. In contrast to both desipramine and chlorimipramine, Org 6582 was devoid of effect on the ability of 1-metaraminol and 6-hydroxydopamine to lower rat heart NA levels. The ability of intraventricularly administered 6-hydroxydopamine to lower rat brain NA levels was unaltered by Org 6582 pretreatment. The corresponding i.p. ED50 values for desipramine and chlorimipramine were 7.3 mg/kg and 28.8 mg/kg respectively. Like desipramine and chlorimipramine, Org 6582 had no effect on the ability of intraventricular 6-hydroxydopamine to lower rat brain DA content. Org 6582 had no effect on steady state levels or on the turnover of NA and DA in the rat brain. It is concluded that Org 6582 is a potent long acting selective inhibitor of 5-HT uptake in vivo.     

Modulation of dopamine release in the nucleus accumbens by 5-HT1B agonists: involvement of the hippocampo-accumbens pathway

Changes in extracellular levels of dopamine (DA), DA metabolites DOPAC and HVA, and the serotonin metabolite 5-HIAA, were measured by microdialysis in the rat nucleus accumbens (n. acc) after treatments with serotonin (5-HT)1A (8-OH-DPAT) or 5-HT1B (RU 24969 and S-CM-GTNH2) receptor agonists. Subcutaneous injections of RU 24969 (0.02-2 mg/kg) dose-dependently decreased 5-HIAA levels (0 to -38%), and also induced long-lasting increases in DA levels (0 to +37%) and DOPAC (+11% at the dose 0.5 mg/kg) in the shell of the n. acc, whereas 8-OH-DPAT (0.25 and 0.5 mg/kg) reduced 5-HIAA levels (-25%) and very slightly increased DOPAC at the lower dose (+4%), but had no effect on DA levels. Three weeks after interruption of the subicular efferent projections, the increase in DA levels previously observed after systemic injections of RU 24969 was abolished. Microinjections of RU 24969 (10 micrograms/microliter) or S-CM-GTNH2 (3 micrograms/microliter) into the ventral subicular area reproduced the effects of systemic injections of RU 24969 cn DA levels and increased DOPAC (+13%; +19%, respectively) and HVA levels (+23%; +24%), with no significant change in 5-HIAA. It is concluded that: (1) serotonin interacts with the mesolimbic dopaminergic system through 5-HT1B, but not 5-HT1A, receptors: and (2) serotonin interaction with the mesolimbic dopaminergic system involves postjunctional 5-HT1B heteroreceptors located in the ventral subicular area, which modulate the activity of glutamatergic hippocampo-accumbens pathways and only secondarily alter DA levels in the n. acc. The possible relevance of these results for schizophrenia is discussed.     

In vitro 2,3,7,8-tetrachlorodibenzo-p-dioxin interference with the anterior pituitary hormone adrenocorticortropin

Pharmacological effects of acute treatment with venlafaxine (VEN), a clinically active antidepressant [a noradrenaline (NA) and 5-hydroxytryptamine (5-HT) reuptake inhibitor without any affinity for neurotransmitter receptors] were studied in mice and rats. VEN inhibited the reserpine- or apomorphine-induced hypothermia and enhanced the L-5-HTP-induced head twitches in mice. It reduced the immobility time in Porsolt's test in mice and rats, but either did not change the locomotor activity (mice) or decreased it (rats). VEN reduced the locomotor hyperactivity induced by amphetamine (AMP), apomorphine (APO) and quinpirole (QUI), as well as the APO-induced stereotypy; the stereotypy induced by AMP in rats was prolonged. VEN neither changed the clonidine-induced aggressiveness in mice nor the behavioral syndrome induced by oxotremorine in rats. The obtained results indicate that VEN, given acutely, shows a pharmacological profile similar to that of tricyclic NA and 5-HT reuptake inhibitors. In contrast to the antidepressants mentioned above, VEN does not exhibit an alpha 1-adrenolytic or a cholinolytic activity (in vivo tests).     

Heterogeneous photobleaching in confocal microscopy caused by differences in refractive index and excitation mode

Changes in brain 5-HT turnover which have been associated with portal-systemic encephalopathy (PSE) in man were studied in rats with experimental PSE for intervals up to 15 weeks following the surgical construction of end-to-side portacaval shunts (PCS). These were compared to changes measured in portacaval transposed rats (PCT) which, show little hepatic dysfunction or cerebral abnormalities but, in common with the PCS rat, sustain total portal-systemic diversion. Thus any differences between these two groups were indicative of hepatic dysfunction and not the systemic diversion of portal blood. After 15 weeks, sustained increases were measured in brainstem and cerebral concentrations of the catabolite of 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), from 0.25+/-0.01 to 0.68+/-0.01*** microg g(-1) brain and from 0.18+/-0.01 to 0.31+/-0.03*** microg g(-1) brain respectively in PCS rats and were statistically greater to those measured in the brainstem and cerebrum of PCT and control rats. Sustained increases in cerebral concentrations alone of 5-hydroxytryptophan (5-HTP), the precursor of 5-HT, from 0.17+/-0.01 to 0.23+/-0.02 microg g(-1) brain were measured in PCS rats and were significantly*** greater than in PCT control rats after 15 weeks. Some early increases in 5-HTP were measured in PCS above control rats but these were not significant after 15 weeks. No sustained significant differences between the 3 groups were measured in 5-HT after 15 weeks. These data confirm previous evidence that the elevations in 5-HTP and 5-HIAA concentrations observed in experimental chronic liver failure and PSE are due to liver dysfunction and not portal-systemic diversion and may contribute additional information regarding the role of derangements in central 5-HT turnover as one of the causes of PSE. ***p<0.001, Newman-Keuls ANOVAR followed by Student's unpaired t-test for individual comparisons, (data shown are mean +/- SEM).     

Changes in the central and peripheral serotonergic system in rats exposed to water-immersion restrained stress and nicotine administration

The effects of water-immersion restraint stress (WS) on chronically nicotine-administered rats were studied in the blood and various regions of the brain. Serotonin (5-HT) levels increased in the hypothalamus, hippocampus, cortex and cerebellum following the administration of nicotine. 5-HT levels increased in all the brain regions following stress. Nicotine decreased stress-induced increased levels of 5-HT in the hippocampus and cerebellum. Nicotine administration alone increased 5-hydroxyindole acetic acid (5-HIAA) levels in the hippocampus and cerebellum. Stress alone also increased 5-HIAA levels in all the brain regions. In the cortex, 5-HT and 5-HIAA levels further increased following the administration of a combination of stress and nicotine compared to rats given stress alone. In the blood as well as in all the brain regions, except the cerebellum, stress or nicotine administration did not affect tryptophan levels. Stress given to nicotine-administered rats resulted in a decrease in tryptophan levels in the blood and plasma. Although 5-HT and 5-HIAA levels were not influenced by stress and/or nicotine administration, the 5-HIAA/5-HT ratio increased in the blood and plasma of rats administered with nicotine and exposed to stress. The effects of nicotine on the serotonergic system depend upon the kind of stress given together with the organs and brain regions involved.     

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.     

Estimation of the functional reserve of the human liver by urinary D-glucaric acid excretion after vitamin C administration

Increased monoamine metabolism in experimental herpes simplex virus (HSV) encephalitis is well established. Both serotonin (5-HT) and dopamine (DA) systems are affected. HSV invades the raphe nuclei after its entry into the brain stem. However, no studies have been published concerning influences of HSV on the neurotransmitters in the raphe. In the present study, concentrations of 5-HT and DA and their metabolites in the raphe nuclei and related brain regions in rabbits with fulminant HSV encephalitis have been analyzed using high-pressure liquid chromatography. Encephalitis was induced by corneal inoculation with HSV. Homovanillic acid (HVA) and dihydroxyphenyl acetic acid (DOPAC) concentrations and HVA/DA ratios were increased in the raphe nuclei suggesting increased DA turnover. The most substantial changes were bilaterally decreased 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the raphe nuclei. The decrease in the raphe 5-HT was reflected also to the projection areas in the hemispheres, where 5-HT concentrations were lower in HSV-inoculated rabbits than in controls. The changes strongly suggest a direct influence of HSV on serotoninergic neurons. Since the ventral parts of the limbic system have rich serotoninergic afferents from the raphe, this also suggests that HSV may reach hemispheres in HSV encephalitis from the brain stem via the ascending serotoninergic system.     

The effect of fenfluramine dosage regimen and reduced food intake on levels of 5-HT in rat brain

Male Wistar rats received fenfluramine in subacute (5 mg/kg b.i.d. i.p. for 4 days) or escalating (0.5, 1, 1.5, 2, 3, 4 and 5 mg/kg b.i.d. i.p., each dose given for 4 days) doses. Saline-treated controls received food ad libitum, or were pair-fed with the fenfluramine-treated animals. Rats were killed 1, 15 and 30 days after drug withdrawal. On day 1, plasma and brain fenfluramine levels were higher, and hypothalamus norfenfluramine levels were lower following escalating compared to subacute dosing, although total active drug levels were unaltered. Both treatment regimes, and pair-feeding reduced food intake and body weight. Subacute fenfluramine reduced brain 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels for up to 30 days. Brain 5-HT and 5-HIAA levels were unaltered following escalating-doses of fenfluramine. Additionally, pair-feeding transiently decreased hippocampal 5-HT levels. These data suggest that escalating-doses of fenfluramine prevent the 5-HT-depleting effect of a sub-cute challenge without altering the anorexic action of the drug.     

Infection- and malignancy-associated hemophagocytic syndromes. Secondary hemophagocytic lymphohistiocytosis

1. The effect of electroconvulsive shock (ECS) on the extracellular concentration of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) was examined in the frontal cortex of rats with the use of in vivo microdialysis. 2. The extracellular concentration of DOPAC, HVA and 5-HIAA was largely increased after the first ECS treatment. The increase after the eighth ECS treatment tended to be attenuated or was significantly attenuated as compared to that after the first ECS treatment. The baseline concentration of DOPAC and 5-HIAA was significantly increased after repeated ECS, though that of DA and HVA did not show any significant change after repeated ECS. 3. These results suggest that the activating effect of repeated ECT on 5-hydroxytryptaminergic (5-HT) and DA neurotransmission, (especially on 5-HT neurotransmission), is significant in improving depression both in patients with Parkinson's disease (PD) and in those who do not suffer from PD.     

High serotonin and 5-hydroxyindoleacetic acid levels in limbic brain regions in a rat model of depression: normalization by chronic antidepressant treatment

Although alterations in serotonin levels and neurotransmission are associated with depressive disorders and effective antidepressant therapy, the exact cause of these disorders and the mode of action of antidepressant drugs are poorly understood. In a genetic rat model of depression [Flinders sensitive line (FSL) rats], deviations from normal serotonin (5-HT) levels and metabolism in specific brain regions were determined. The levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in tissue punches of various brain regions were quantitated simultaneously with an HPLC apparatus coupled to an electrochemical detector. In the nucleus accumbens, prefrontal cortex, hippocampus, and hypothalamus of FSL rats, the levels of 5-HT and 5-HIAA were three- to eightfold higher than in control Sprague-Dawley rats. Significant differences in the levels of 5-HT and 5-HIAA in the striatum and raphe nucleus of the "depressed" and normal rats were not observed. After chronic treatment with the antidepressant desipramine (5 mg/kg/day for 18 days), the immobility score in a swim test, as a measure of a behavioral deficit, and 5-HT levels of the FSL rats became normalized, but these parameters in the control rats did not change. The [5-HIAA]/[5-HT] ratio was lower in the nucleus accumbens and hypothalamus of the FSL than in the control rats, and increased after desipramine treatment only in the nucleus accumbens of the FSL rats. These results indicate that the behavioral deficits expressed in the FSL model for depression correlate with increased 5-HT levels in specific limbic sites and suggest the FSL rats as a novel model for clarification of the molecular mechanism of clinically used antidepressant drugs.     

Hypertension in paediatrics: can pre- and post-captopril technetium-99m dimercaptosuccinic acid renal scans exclude renovascular disease?

The presence of biogene monoamines in adult and larval Diphyllobothrium dendriticum (Cestoda) was investigated by high-performance liquid chromatography with electrochemical detection (HPLC-ED). The biogene amines serotonin (5-HT), dopamine (DA), noradrenaline (NA), and adrenaline (A) as well as many of their precursors and metabolites, comprising a total of 15 different substances, were analyzed. 5-HT, DOPA, DA, NA, and A were detected in the worm, with 5-HT, DOPA, and DA being the dominating amines. The DA metabolites DOPAC and 3-MT or the 5-HT precursor 5-hydroxytryptophan could not be detected, but two unidentified substances, believed to be catecholic, were present in the worm. A high concentration of DOPA was measured in the proglottids and especially in the eggs. This is the first report of A in a flatworm.     

Effect of anoxia on striatal monoamine metabolism in immature rat brain compared with that of hypoxia: an in vivo microdialysis study

We examined in 5-day-old rats the effects of either anoxia or 8% hypoxia on extracellular monoamines such as dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine (NE), 5-hydroxytryptamine (5-HT), and 5-hydroxyindole-3-acetic acid (5-HIAA) using in vivo microdialysis and subsequent HPLC. After stabilization 64 animals were exposed to 100% nitrogen for 16 min and 40 animals to 8% oxygen for 128 min. Both anoxia and hypoxia produced acute increase in the striatal extracellular DA (anoxia: P < 0.001, hypoxia: P < 0.01). Especially in anoxia, DA levels increased transiently to 2000-times the basal levels and 6-times higher than those in hypoxia. NE also increased in both anoxia and hypoxia. DOPAC and HVA decreased during hypoxia (P < 0.01 and P < 0.001, respectively), while those in anoxia were unchanged. In anoxia, decrease tendency of their levels were in short duration and that of 5-HIAA was followed by gradual increase (P < 0.001). These data demonstrated that brief exposure to anoxia or hypoxia had significant influence on striatal monoamine metabolism in immature brain and the pattern of change of monoamine in anoxia was different from that in hypoxia.     

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.     

Biotransformation of locally applied precursors of dopamine, serotonin and noradrenaline in striatum and hippocampus: a microdialysis study

In vivo microdialysis in freely moving rats was used to study the biotransformation, consisting primarily of decarboxylation by aromatic amino acid decarboxylase (AAAD), of the precursors L-3,4-dihydroxyphenylalanine (L-DOPA), L-5-hydroxytryptophan (L-5HTP), and L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) on extracellular levels of dopamine (DA), serotonin (5HT) and noradrenaline (NA), respectively. The precursors were administered locally through the microdialysis probe into the striatum and into the hippocampus. The different transmitter systems were compared with respect to the ability of the precursors to elevate extracellular levels of their associated transmitter. The basal extracellular concentrations of NA and DA were found to be tetrodotoxin (TTX, a blocker of fast sodium channels) sensitive in striatum and hippocampus, indicating the neuronal origin of the measured transmitters. The extracellular concentrations of 5HT (in hippocampus) were only 60% TTX-sensitive. L-DOPA and L-5HTP showed to be effective precursors of DA and 5HT, respectively, although their formation profile was quite different. The L-DOPA-induced increase in extracellular DA was large and short-lasting, while the L-5HTP-induced increase in 5HT was slower and less pronounced. The relative increase in extracellular DA or 5HT was more pronounced in the brain region where their baseline values were lower, but the absolute amount of transmitter formed from their precursor was similar in both brain regions. L-threo-DOPS was a poor precursor for NA and also failed to influence extracellular DA in striatum, questioning its use in the treatment of freezing gait in late stages of Parkinson's disease.