Neurochemical changes in pigeon cerebrospinal fluid during chronic administration of buspirone or 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)

Cerebrospinal fluid (CSF), collected repeatedly from White Carneau pigeons chronically implanted with guide cannulae located in the lateral ventricles, was analyzed for metabolites of serotonin, dopamine and norepinephrine after acute and chronic administration of buspirone or 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Following the acute administration of 3.0 mg/kg buspirone, levels of 5-hydroxyindoleacetic acid (5-HIAA) decreased, while increases occurred in the dopamine metabolites homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC). Decreases in 5-HIAA persisted throughout the chronic dosing regimen (36 days), while dopamine metabolites returned to control levels within 8 days. When chronic buspirone was discontinued, levels of 5-HIAA were restored to predrug control levels, while levels of HVA, DOPAC and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) decreased. All metabolites returned to predrug control levels within one week following buspirone discontinuation except for MHPG, which remained depressed. When the acute effects of buspirone were reexamined, levels of 5-HIAA were again significantly decreased, while HVA and DOPAC levels, as well as those of MHPG, increased significantly. Acute administration of the 5-HT1A receptor ligand 8-OH-DPAT (3.0 mg/kg) resulted in large decreases in 5-HIAA levels that persisted throughout the period of chronic administration. Neither acute nor daily administration of 8-OH-DPAT changed levels of HVA, DOPAC or MHPG. Large increases in 5-HIAA occurred when chronic 8-OH-DPAT was discontinued but declined within one week to control levels. Following a two-week drug-free period, 8-OH-DPAT again caused a significant reduction in 5-HIAA levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bilateral neurochemical changes induced by unilateral cerebral haloperidol administration: evidence for cerebral asymmetry in the rat.

Bilateral alterations in dopamine metabolism were determined in the striatum, olfactory tubercle, and frontal cortex of rats pretested for circling behavior. Dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine, and 5-hydroxyindole-3-acetic acid (5-HIAA) were measured by high-performance liquid chromatography 15 min after right or left intracarotid infusion of haloperidol. Concentrations of DOPAC and HVA were significantly increased in the striatum and frontal cortex ipsilateral to the side of haloperidol infusion, regardless of whether it was right or left. In contrast, the concentrations of these metabolites were unchanged in the olfactory tubercle after a right side infusion, but bilateral increases were evident after a left side infusion. Higher levels of DOPAC and HVA were also apparent in the left striatum and olfactory tubercle after intravenous jugular administration of haloperidol. Dopamine levels were significantly lower in the left striatum and right olfactory tubercle after intravenous haloperidol infusions. 5-HIAA concentrations were higher in the left olfactory tubercle following left side infusions of haloperidol. These data indicate that unilateral cerebral administration of haloperidol induces asymmetric and side-dependent alterations in dopamine and serotonin metabolites. These differences appear to be due to intrinsic variations in the sensitivity to haloperidol, but are not associated with the direction of circling behavior.     

Analysis of extracellular DOPAC, HVA and 5-HIAA in rat striatum in vivo by differential pulse voltammetry: effect of phencyclidine, haloperidol and their coadministration

Phencyclidine (PCP, 10 mg/kg s.c.) produced a marked reduction in the extracellular concentrations of DOPAC and HVA in the rat striatum in vivo, as measured by differential pulse voltammetry. In contrast, extracellular 5-HIAA levels were significantly elevated. Haloperidol (1 mg/kg i.p.) increased DOPAC and HVA, and reduced 5-HIAA, in agreement with previous studies. When PCP and haloperidol were injected together, the effects of PCP were abolished. These results suggest that PCP administration leads to increased activation of dopamine receptors, which results in a decrease in striatal dopamine turnover and an increase in striatal serotonin turnover.     

The dopamine-serotonin relationship in clozapine response

The effects of clozapine on the dopamine and serotonin systems may underlie its atypical pharmacologic and clinical profile. To examine this hypothesis, we measured dopamine and serotonin plasma and cerebrospinal (CSF) metabolites and the relationship of these values to treatment response in 19 neuroleptic refractory and intolerant schizophrenic patients. Only a small change in the CSF and plasma homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) levels was found. However, the pretreatment CSF HVA/5HIAA ratio and, to a lesser extent, the CSF HVA level predicted treatment response. These results suggest that the modest relationship between HVA and 5-HIAA and treatment response supports the involvement of both neurotransmitters in the pathophysiology of schizophrenia.     

Effects of trepelennamine on brain monoamine turnover in morphine dependent and abstinent mice

Previous studies have reported that the histamine H₁ receptor blocker tripelennamine potentiates morphine withdrawal. In this paper, the in vivo effects produced by tripelennamine on the turnover of serotonin (5-HT), dopamine (DA) and noradrenaline (NA) in the whole brain, excluding the cerebellum, were studied in control, morphine-dependent (by SC implantation of a 75 mg morphine pellet) and morphine-dependent male CD1 mice just before naloxone-precipitated withdrawal. Tripelennamine (1–10 mg/kg) was administered SC 45 min before the animals were killed. Serotonin, 5-hydroxyindole-3-acetic acid (5-HIAA), dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and noradrenaline were measured by high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD) and 3-methoxy-4-hydroxyphenylethyl-eneglycol (MHPG) was measured by HPLC coupled with fluorimetric detection. Ratios 5-HIAA/5-HT, DOPAC + HVA/DA and MHPG/NA were taken as an index of serotonin, dopamine and noradrenaline turnovers, respectively. Tripelennamine (1 and 10 mg/kg) significantly reduced serotonin turnover in control and morphine-dependent mice, and potentiated the serotonin turnover reduction when it was administered 30 min before naloxone injection. The dopamine turnover was diminished by tripelennamine (1 and 10 mg/kg) in the morphine-dependent group. Tripelennamine (10 mg/kg) reduced noradrenaline turnover during abstinence. These results suggest that the potentiation of opiate abstinence by tripelennamine could be related to its antiserotonergic profile.     

Behavioral sensitization to quinpirole is not associated with increased nucleus accumbens dopamine overflow

This study assessed the relationship between extracellular nucleus accumbens (NAc) dopamine (DA) concentrations and sensitized locomotor activation following repeated administration of the DA D2-like receptor agonist quinpirole. Locomotor activity measures and nucleus accumbens microdialysis samples were collected concurrently in response to the first (acute) and tenth (repeated) quinpirole injection (0.5 mg/kg s.c., every other day). Results indicate that acute quinpirole produced locomotor activation and that repeated quinpirole resulted in locomotor sensitization. Acute quinpirole significantly decreased the detection of extracellular concentrations of DA and the DA metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the NAc. Following repeated quinpirole, basal NAc DA levels were decreased, whereas basal DOPAC levels were increased. Nevertheless, quinpirole challenge elicited a significant decrease in DA, DOPAC and HVA following repeated treatment. In addition, although acute quinpirole did not affect NAc levels of the serotonin metabolite 5-hydroxyindolacetic acid (5-HIAA), quinpirole challenge produced a significant increase in 5-HIAA levels following repeated treatment. Taken together, these data indicate that functional DA autoreceptor subsensitivity is not a necessary condition for the expression of behavioral sensitization to quinpirole. Instead, it appears that behavioral sensitization to quinpirole occurs predominantly as a consequence of neuroadaptations that are post-synaptic to DA release.     

Differential effects of clorgyline on catecholamine and indoleamine metabolites in the cerebrospinal fluid of rhesus monkeys

The effects of acute and chronic administration of clorgyline, an irreversible inhibitor of monoamine oxidase type A (MAO-A), on the deaminated metabolites of norepinephrine, dopamine and serotonin were examined in rhesus monkey cerebrospinal fluid (CSF). Acute clorgyline treatment resulted in highly significant, dose-dependent reductions in 3-methoxy-4-hydroxyphenylglycol (MHPG) of 50% (1 mg/kg) and 68% (2 mg/kg) compared to pretreatment values. Chronic clorgyline administration (0.25 to 0.5 mg/kg X 24 days) resulted in a 67% reduction in CSF MHPG. In contrast, the concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were less affected by acute clorgyline administration, being reduced significantly only after the 2 mg/kg dose, which lowered 5-HIAA 27% and HVA 48%. Chronic clorgyline treatment had no significant effect on the CSF concentrations of HVA and 5-HIAA. These data, which suggest that MAO-A inhibition by clorgyline in vivo is more closely associated with changes in the noradrenergic than the serotonergic or dopaminergic systems in nonhuman primates, are in general agreement with the effects of clorgyline on CSF and urinary biogenic amine metabolites in man. They differ from several in vitro studies which indicate a primary role of MAO-A in the metabolism of serotonin and of MAO-B in norepinephrine degradation in primate brain. The discrepancies may reflect modulating effects of synaptic feedback mechanisms on the actions of clorgyline in vivo or perhaps a failure of CSF metabolites to adequately reflect brain amine metabolism changes. The lack of change in platelet MAO-B activity during clorgyline treatment together with the minimal changes in HVA concentrations indicate that the selective inhibitory effects of clorgyline on MAO-A were maintained during chronic administration of low drug doses.     

Decrease in dopamine,its metabolites and noradrenaline in cerebrospinal fluid of schizophrenic patients after withdrawal of long-term neuroleptic treatment

Dopamine (DA), homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), noradrenaline (NA), and 5-hydroxyindolacetic acid (5HIAA) were measured in cerebrospinal fluid (CSF) of 15 chronic schizophrenic patients before and 2 weeks after withdrawal of long-term neuroleptic treatment. Total neuroleptic-like activity in serum (NLA) was determined at the same times. Levels of DA and its metabolites (DOPAC and HVA) and NA were significantly reduced after the discontinuation of neuroleptic treatment. No change was observed in 5HIAA values. NLA was substantially reduced, but still remained detectable. The decrease in DA, DOPAC, and HVA all showed positive correlations with each other, and correlated negatively with NLA measured after 2 weeks. Our data implies that the decrease in DA turnover is the result of the discontinuance of DA receptor blockade, while the change in NA level is independent of it.This work was supported by the State Office for Technical Development, Hungary     

The effect of olanzapine treatment on monoamine metabolite concentrations in the cerebrospinal fluid of schizophrenic patients.

The mechanism of action of both typical antipsychotics and the atypical antipsychotic, clozapine, may be related to the (changing) interaction of dopamine and serotonin in schizophrenia. This study examined the effect of olanzapine in schizophrenic patients on cerebrospinal fluid (CSF) metabolites of dopamine (homovanillic acid, HVA) and serotonin (5-hydroxyindoleacetic acid, 5-HIAA). Twenty-three male schizophrenic patients, who were drug-free for at least 2 weeks (mean drug-free period of 35 days +/- 43; median 16 days), underwent a lumbar puncture (LP). Patients were subsequently treated with olanzapine 10 mg/day for 6 weeks, after which the LP was repeated. CSF was assayed for HVA and 5-HIAA concentrations. Psychiatric symptoms were rated once a week. Olanzapine significantly increased HVA concentrations and the HVA/5-HIAA ratio while 5-HIAA concentrations were not altered. These changes did not significantly correlate with treatment response. A negative correlation was found between HVA concentrations and negative symptoms after olanzapine treatment. In conclusion, olanzapine treatment increases HVA concentrations and the HVA/5-HIAA ratio in CSF of schizophrenic patients, but these changes are unrelated to its clinical efficacy.     

Effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on biogenic amines and their acidic metabolites in brain and cerebrospinal fluid of rats

Effects of single subcutaneous doses of sodium 2,4-dichlorophenoxyacetate (2,4-D-Na) on biogenic amines and their acidic metabolites in rat brain and cerebrospinal fluid (CSF) were analyzed by high pressure liquid chromatography. After 200 mg/kg 2,4-D-Na, the cerebral concentration of 5-hydroxytryptamine (5-HT) was increased slightly and that of 5-hydroxyindoleacetic acid (5-HIAA) roughly 3-fold between 1 and 8 h after the administration. There was also a tendency towards slightly lowered dopamine (DA) levels. No statistically significant changes in brain concentrations of noradrenaline (NA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) or tryptophan (TRY) were found. At the same time, however, the maximal increase in DOPAC, HVA and 5-HIAA concentrations in the CSF was 2.3–5.8-fold. The dependency of biogenic amines and metabolites on 2,4-D-Na dose was studied by injecting s.c. 0, 10, 30 and 100 mg/kg and sacrificing the rats at 2 h. In the brain, there was a dose-dependent increase in concentrations of 5-HIAA (at the two highest doses) and HVA (at the highest dose) while in the CSF those of all three acidic metabolites increased at the two highest doses. The 10 mg/kg dose had no effect. The results agree with the hypothesis that 2,4-D inhibits the organic acid transport out of the brain, which should then result in increased cerebral levels of acidic metabolites of biogenic amines, but it may also have effects on the activity of serotoninergic and dopaminergic neurones.     

The effects of kainic acid lesions on dopaminergic responses to haloperidol and clozapine

The antipsychotic drugs haloperidol and clozapine have the common action of increasing dopamine metabolism in the striatum (nucleus accumbens, caudate-putamen) of the rat. Intracerebroventricular administration of kainic acid (KA) produces neuronal loss in limbic-cortical brain regions which project directly or indirectly to the striatum. In the present study, dopamine metabolism in subregions of the striatum was examined in rats with KA lesions after acute and chronic haloperidol or clozapine administration. The main findings was that the elevating effect of acute haloperidol treatment on the dopamine metabolite, DOPAC, was blocked in the nucleus accumbens shell and diminished in medial and laterodorsal caudate-putamen of the KA-lesioned rats. In addition, the elevating effects of both acute and chronic haloperidol treatment on dopamine turnover were attenuated in the laterodorsal caudate-putamen of KA-lesioned rats. The levels of dopamine, DOPAC, and HVA after chronic clozapine treatment were greater in KA-lesioned than control rats. These results indicate that dopaminergic responses to haloperidol may be diminished by limbic-cortical neuropathology, while such pathology does not significantly alter dopaminergic responses to clozapine. Received: 30 September 1996 / Final version: 6 March 1997     

Neurochemistry of withdrawal emergent symptoms in children

The probenecid procedure was used to study the metabolite accumulations of dopamine (DA) and serotonin (5-HT) in the cerebrospinal fluid (CSF) of 11 children receiving chronic neuroleptic therapy. Specimens were obtained while the children were being given chronically prescribed medication (Condition 1) and again 3–4 weeks later, following the discontinuation of drugs (Condition 2). At that time, five children showed typical dyskinetic withdrawal emergent symptoms (WES) and six were free of symptoms. CSF specimens were also obtained from eight drug-free children, diagnosed as having chronic organic brain disease, who served as a contrast population against which the findings were evaluated. CSF accumulations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) did not differentiate the drug-treated children who showed WES from those who did not manifest these symptoms. A significant decrease in 5-HIAA was found in Condition 2, suggesting that chronic treatment with neuroleptics may effect 5-HT metabolism in children. The contrast population was found to have lower CSF concentrations of probenecid and were consequently of little help in clarifying the nature of the 5-HIAA decrement. A number of serious deficiences were noted regarding the use of the probenecid procedure, and it is felt that the use of spinal taps for studying neuroleptic effects on brain metabolism in children is unlikely to provide important information with regard to either CNS drug actions or toxicity.     

Systemic sulpiride increases dopamine metabolites in the lateral hypothalamus.

In rats with microdialysis probes in the perifornical lateral hypothalamus (PFH) a single injection of the D2 receptor blocker 1-sulpiride (20 mg/kg IP) significantly increased extracellular dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), but not 5-hydroxyindoleacetic acid (5-HIAA). This suggests that sulpiride crosses the blood-brain barrier and blocks D2 dopamine receptors in the PFH leading to increased dopamine turnover reflected in increased extracellular DOPAC and HVA. We conclude that D2 blockade in the hypothalamus could play a role in the hyperphagia and body weight gain observed in female rats under chronic administration of the antipsychotic drug, sulpiride.     

Effects of acute ethanol administration on monoamine and metabolite content in forebrain regions of ethanol-tolerant and -nontolerant alcohol-preferring (P) rats

The contents of dopamine (DA), serotonin (5-HT) and their metabolites in the frontal cortex, anterior striatum, nucleus accumbens and hypothalamus of alcohol-tolerant and -nontolerant rats of the alcohol-preferring P line were determined one hour after the IP administration of 2.5 g ethanol/kg body wt. Compared with saline-injected controls, nontolerant P-rats injected with ethanol had (a) 60% higher levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the frontal cortex; (b) 30-60% higher levels of DOPAC and HVA in the anterior striatum and nucleus accumbens; and (c) 20% higher levels of 5-HIAA in all three forebrain regions. In the tolerant group, the effects of IP ethanol on DOPAC and HVA were markedly attenuated or completely eliminated in these three forebrain regions. However, in the case of 5-HIAA, an attenuated response was observed only in the nucleus accumbens of the tolerant group. The IP administration of ethanol had little effect on the contents of DA or 5-HT in any of these three forebrain regions, with the exception that 5-HT levels were elevated in the anterior striatum of both the tolerant and nontolerant groups. In the hypothalamus, there were no significant differences for the contents of DA, 5-HT or their metabolites between the nontolerant or tolerant P rats after IP ethanol. The data indicate that both acute ethanol administration and chronic alcohol intake by the P line of rats alters certain DA and 5-HT systems that may be involved in the brain reward circuitry and in DA pathways involved in motor functions.     

Reduced metabolism and turnover rates of rat brain dopamine, norepinephrine and serotonin by chronic desipramine and zimelidine treatments

As part of of an ongoing effort to compare changes in whole body turnover of catecholamines and serotonin in man with those induced by antidepressants in the rat brain, we have evaluated the chronic effects of desipramine (DMI) and zimelidine (ZMI) on brain catecholamines and serotonin in the rat. The amines and metabolites measured include norepinephrine (NE), dopamine (DA) and their metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Three brain areas were analysed; the hypothalamus, caudate nucleus and frontal cortex. Chronic DMI and ZMI reduced hypothalamic MHPG and caudate nucleus DA metabolites, in particular HVA. Both drugs reduced NE and DA turnover rates (estimated after alpha-methyl-p-tyrosine injection) and the rate of MHPG formation in the hypothalamus (estimated after pargyline treatment). They did not change NE turnover rate, but reduced DA turnover rate and rate of HVA formation in the caudate nucleus. Chronic DMI but not ZMI reduced DOPAC rate of formation in the caudate nucleus. Apparently changes in DA turnover and metabolism produced by these antidepressants are better related to changes in HVA than DOPAC concentrations. Similar to their influence on hypothalamic and caudate nucleus catecholamines, both chronic DMI and ZMI produced changes in serotonin concentration in the caudate nucleus and frontal cortex serotonin that suggest a reduction in its turnover rate and metabolism. The reduction in NE turnover in hypothalamus is consistent with the effects of chronic DMI and ZMI on whole body NE turnover observed in man.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of harmine on dopamine output and metabolism in rat striatum: role of monoamine oxidase-A inhibition

In vivo microdialysis was used to investigate the effects of acute injections of harmine on extracellular concentrations of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxindoleacetic acid (5-HIAA) in the striatum of awake rats. Administration of harmine in doses of 0.5, 2.5, and 10 mg/kg (i.p.) elicited a dose-dependent increase of the dopamine efflux to 152, 173, and 243% and a decrease in DOPAC to 52, 36, and 10%, and HVA to 67, 45, and 20% throughout, respectively; 5-HIAA concentrations were decreased to 81, 74, and 72% only. In contrast to D-amphetamine, which also increases dopamine release and decreases its metabolites, the stimulatory action of harmine on dopamine release in the striatum was totally abolished in the presence of tetrodotoxin (1 microM). Similar to monoamine oxidase (MAO)-A inhibitors, harmine potentiated the stimulatory effect of D-amphetamine (10 microM), infused by reverse microdialysis in the striatum, on dopamine release. Pre-treatment with the benzodiazepine receptor antagonist flumazenil (5 mg/kg, i.p.) did not modulate the effect of harmine on striatal dopamine release and metabolism. Administration of the reversible MAO-A inhibitor, moclobemide (20 mg/kg, i.p.), induced an increase in dopamine to 256% and a decrease in DOPAC, HVA, and 5-HIAA to 30, 24, and 62%, respectively, reproducing a pattern similar to that of harmine. Taken together, these results indicate that harmine affects the brain dopamine system probably by acting as a MAO-A inhibitor and not as an inverse agonist for the benzodiazepine receptors.     

Effects of acute cannabis use on urinary neurotransmitter metabolites and cyclic nucleotides in man

The noradrenaline, dopamine and serotonin metabolites methoxy-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), as well as the cyclic nucleotides c-AMP and c-GMP were estimated in urine samples of five normal volunteers. Ten control samples and two samples after cannabis use were analyzed for each volunteer. Cannabis use caused significant decreases in MHPG and c-AMP, and increases in HVA, while 5-HIAA and c-GMP excretion remained unchanged. The results indicate that cannabis use interferes with catecholaminergic mechanisms in man, decreasing the noradrenaline and increasing dopamine turnover, probably through action on presynaptic receptors.     

Diminished catalepsy and dopamine metabolism distinguish aripiprazole from haloperidol or risperidone

Catalepsy and changes in striatal and limbic dopamine metabolism were investigated in mice after oral administration of aripiprazole, haloperidol, and risperidone. Catalepsy duration decreased with chronic (21 day) aripiprazole compared with acute (single dose) treatment across a wide dose range, whereas catalepsy duration persisted with chronic haloperidol treatment. At the time of maximal catalepsy, acute aripiprazole did not alter neostriatal dopamine metabolite/dopamine ratios or homovanillic acid (HVA) levels, and produced small increases in dihydroxyphenylacetic acid (DOPAC). Effects were similar in the olfactory tubercle. Dopamine metabolism was essentially unchanged in both regions after chronic aripiprazole. Acute treatments with haloperidol or risperidone elevated DOPAC, HVA, and metabolite/dopamine ratios in both brain areas and these remained elevated with chronic treatment. The subtle effects of aripiprazole on striatal and limbic dopamine metabolism, and the decrease in catalepsy with chronic administration, illustrate fundamental differences in dopamine neurochemical actions and behavioral sequelae of aripiprazole compared to haloperidol or risperidone.     

Assessment of cerebrospinal fluid levels of dopamine metabolites by gas chromatography

The acid metabolites of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were determined in lumbar cerebrospinal fluid (CSF) by a new procedure. After gas Chromatographic separation, the pentafluoropropionyl 2,2,3,3,3-pentafluoro-1-propionyl esters of DOPAC and HVA were analyzed by electron capture detection. Normal HVA levels were quantitated in as little as 0.1 ml CSF. No significant amounts of DOPAC (< 1 ng/ml) were found in any of the drug-free samples analyzed. Levels of DOPAC increased only marginally in the CSF of patients receiving acute or chronic doses of lDopa. Baseline HVA levels ranged from 4.5–50 ng/ml with a mean value of 23 ng/ml. These studies demonstrate that HVA is the major dopamine metabolite in human CSF.Supported by a grant from the NIMH No. MH 21638-03 and a Research career development award No. 1 K04 GM 40793-05 to S. W.     

吡喹酮对大鼠单胺介质的影响

吡喹酮是一种新型广谱抗寄生虫药。本文报道用高效液相色谱-电化学检测器联用的方法,测定单胺类神经介质及其代谢物的含量,研究吡喹酮对大鼠单胺类介质的影响。结果表明:吡喹酮(250 mg/kg使脑DA的酸性代谢产物DOPAC,HVA和5-HT的代谢物5-HIAA的含量明显升高,而对DA和NA含量无明显影响。DA酸性代谢物和5-HIAA升高表明吡喹酮能增加DA和5-HT的转换率。