针刺对肥胖大鼠中缝核群作用的探讨

目的 :观察针刺对肥胖大鼠中缝核群的作用。方法 :采用中枢神经核团推挽灌流和生化实验技术 ,研究针刺对肥胖大鼠中缝核群组织单胺类递质水平的影响。结果 :肥胖组中缝核群中色氨酸 (Trp)、5-羟色胺 (5- HT)、5- TH/ 5-羟吲哚乙酸 (5- HIAA)、酪氨酸 (Tyr)水平显著低于正常组 ,而去甲肾上腺素 (NA)、多巴胺 (DA)含量却显著高于正常组。中缝背核中 5- HT含量与肥胖程度呈负相关。针刺与肥胖组相比 ,中缝核群中 5- HT含量显著回升 ,DA含量明显回降。说明针刺对肥胖机体中缝核群单胺类递质具有良性调整作用。结论 :针刺对肥胖机体中缝核群的调控可能是针刺减肥关键因素之一。     

Clinical and biochemical responses to therapy in Alzheimer's disease and multi-infarct dementia

Summary Memory performance, central monoaminergic function and sympathetic nerve activity were studied in patients with dementia of the Alzheimer type (DAT) or with multi-infarct dementia before and after 4 weeks with single or combined drug therapy (choline-piracetam). Analysis of the levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), 3-methoxy-4-hydroxyphenylacetic acid (HVA) and 5-hydroxyindolacetic acid in the cerebrospinal fluid (CSF) and also in urine (plus 3-methoxy-4-hydroxy mandelic acid) showed that the basal values of HVA in the CSF and urine were lower in the more severely demented compared with the mildly demented subjects in both groups. The combined drug treatment resulted in a statistically significant increase in the MHPG level in the CSF of mildly demented subjects of the DAT group, while it seemed not to influence the other monoamine metabolites. The sympathetic nerve activity was similar in both patient groups and was unchanged after therapy. These findings suggest a dopaminergic deficit in advanced stages of the disease and a possible enhancement of the central noradrenergic output with therapy. No effects of therapy on memory performance or correlations between monoamine levels and memory test scores were noted.     

Distribution of serotonin in the caudal neurosecretory complex A light and electron microscopic study

Summary The caudal neurosecretory complex (CNc) of poecilids has previously been shown to receive serotonergic inputs. In the present study, immunohistochemical techniques were applied at the light and electron microscopic levels to characterize serotonergic terminals in the neuroendocrine nucleus. A dense plexus of varicose fibers observed in the rostral CNc neuropil was absent in the spinal cords of deafferented fish, indicating that the origin of this input was extranuclear. Ultrastructural study revealed no direct contacts between labeled structures and neuroendocrine cells. Non-synaptic terminals (varicosities) were the predominantly labeled structures in the neuropil. Synaptic terminals were observed on cellular and axonal targets in the CNc. Small cells containing 70 nm dense-core vesicles received serotonergic input on their perikarya. Labeled synapses were also found on unlabeled axon terminals which made axoaxonal synapses on neuroendocrine processes. Non-synaptic terminals may be responsible for a variety of serotonin-mediated effects in the CNc. Synaptic interactions with local catecholaminergic and afferent cholinergic inputs to the CNc are likely.     

Evaluation of the effects of a specific α2-adrenoceptor antagonist, atipamezole, on α1- and α2-adrenoceptor subtype binding, brain neurochemistry and behaviour in comparison with yohimbine

In the present study we evaluated the α₁- and α₂-adrenoceptor subtype binding, central α₂-adrenoceptor antagonist potency, as well as effects on brain neurochemistry and behavioural pharmacology of two α₂-adrenoceptor antagonists, atipamezole and yohimbine. Atipamezole had higher selectivity for α₂- vs. α₁-adrenoceptors than yohimbine regardless of the subtypes studied. Both compounds had comparable affinity for the α_2A-, α_2C- and α_2B-adrenoceptors, but yohimbine had significantly lower affinity for the α_2D-subtype. This may account for the fact that significantly higher doses of yohimbine than atipamezole were needed for reversal of α₂-agonist (medetomidine) -induced effects in rats (mydriasis) and mice (sedation and hypothermia). The effect on central monoaminergic activity was estimated by measuring the concentrations of transmitters and their main metabolites in whole brain homogenate. At equally effective α₂-antagonising doses in the rat mydriasis model, both drugs stimulated central noradrenaline turnover (as reflected by increase in metabolite levels) to the same extent. Atipamezole increased dopaminergic activity only slightly, whereas yohimbine elevated central dopamine but decreased central 5-hydroxytryptamine turnover rates. In behavioural tests, atipamezole (0.1–10 mg/kg) did not affect motor activity but stimulated food rewarded operant (FR-10) responding (0.03–3 mg/kg) whereas yohimbine both stimulated (1 mg/kg) and decreased (≥ 3 mg/kg) behaviour in a narrow dose range in these tests. In the staircase test, both antagonists increased neophobia, but in the two compartment test only yohimbine (≥ 3 mg/kg) decreased exploratory behaviour. The dissimilar effects of the antagonists on neurochemistry and behaviour are thought to be caused by non α₂-adrenoceptor properties of yohimbine. In conclusion, the α₂-antagonist atipamezole blocked all α₂-adrenoceptor subtypes at low doses, stimulated central noradrenergic activity and had only slight effects on behaviour under familiar conditions, but increased neophobia. The low affinity for the α_2D-adrenoceptor combined with its unspecific effects complicates the use of yohimbine as pharmacological tool to study α₂-adrenoceptor physiology and pharmacology. Received: 20 May 1997 / Accepted: 29 July 1997     

Neurochemical effects of minaprine,a novel psychotropic drug,on the central cholinergic system of the rat

Minaprine, a novel psychotropic drug with antidepressant, anticataleptic and antiaggressive properties, produced an increase in rat brain regional acetylcholine content at a subconvulsant dose of 30 mg/kg IP. The greatest increase (60%) was produced in the striatum, whereas an increase of about 35% was obtained in the hippocampus and the rest of the cortex. A small but significant increase of 14% was also found in the midbrain-hindbrain region. Minaprine decreased choline content only in the striatum. No tolerance to acute challenge was observed after 10-day chronic treatment. In vitro, the drug had no effect on striatal choline acetyltransferase activity up to a concentration of 160 M and only weakly displaced (³H) dexetimide from its specific muscarinic receptor binding sites in striatum (IC₅₀, 2×10^-4 M). After in vivo administration the drug did not affect sodium-dependent high affinity choline uptake by a hippocampal homogenate. On the other hand, the drug inhibited both striatal and hippocampal acetylcholinesterase activity at high (40–160 M) concentrations in vitro. In vivo the drug produced a brief (5 min), small (18%) decrease in the enzymic activity which corresponded in time to the peak drug level attained in the brain, but was not concomitant with a change in striatal acetylcholine content. By contrast, the increase in striatal acetylcholine appeared after 30 min when there was no longer inhibition of acetylcholinesterase activity and when the level of minaprine in brain was reduced by 78%. Blockade of dopamine receptors by pimozide pretreatment partially prevented the increase in striatal acetylcholine produced by minaprine, whereas interference with cholinergic or serontonergic neurotransmission was without effect. The data suggest that minaprine acts partially as a dopaminergic agonist in increasing striatal acetylcholine content. The possibility that an active metabolite of minaprine is responsible for a more direct effect of the drug at the cholinergic neurons is discussed.     

The putatively antipsychotic agent amperozide produces behavioural stimulation in the rat

Summary Amperozide (FG 5606; N-ethyl-4-[4,4-bis(p-fluorophenyl) butyl]-1-piperazinecarboximide) is a new putatively antipsychotic compound with a postulated 5-HT₂ antagonistic profile. Somewhat surprisingly amperozide dose dependently induced a behavioural stimulation in reserpinized and in nonpretreated rats. The behaviour consisted of both forward and backward locomotion as well as forepaw circling and a grooming like behaviour. Since the behavioural pattern clearly differ from that produced by classical dopaminergic or serotonergic agonists (e. g. apomorphine or 8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT), and has not been previously reported, we decided to investigate the origin of this effect.In the behavioural paradigms it was not possible to antagonize the amperozide stimulation in reserpinized rats with the dopamine receptor blockers haloperidol, raclopride or R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine, SCH 23390. Neither the 5-HT₂ receptor blocking agent ritanserin nor the tryptophan and tyrosine hydroxylase inhibitor DL-3,4-dihydroxy-phenyl--propylacetamide, H22/54, could block the motoric stimulation or the forepaw circling behaviour produced by amperozide. However, the noradrenaline synthesis inhibitor bis- (4-methyl-1-homopiperazinylthiocarbonyl)-disulfide, FLA 63, as well as the -adrenoceptor antagonist phenoxy-benzamine, could partly inhibit the locomotor stimulation. Hence, noradrenaline seems to be, at least in part, involved in the behavioural stimulatory effect of amperozide. synthesis rate (DOPA formation) in normal or reserpinized animals in the striatal or the limbic brain regions. In reserpinized animals amperozide also failed to antagonize the decrease in DOPA formation after apomorphine and 3-hydroxy-benzylhydrazine HCl, NSD 1015, in these regions. Thus, amperozide failed to show agonistic or antagonistic action on central dopamine receptors. However, in the noradrenaline rich cortical region amperozide induced an increase in DOPA accumulation. The compound also increased the levels of normetanephrine as well as antagonized the decrease in DOPA accumulation by clonidine in the cortical brain region. Amperozide also increased the disappearence rate of noradrenaline after inhibitor of tyrosine hydroxylase by -methyl-para-tyrosine. These data suggest that, biochemically, amperozide has got ₂ antagonistic properties. However, it is not evident that these biochemical properties are responsible for the behavioural effects of amperozide. Send offprint requests to Nicholas Waters at the above addressParts of this work were presented at the Society for Neuroscience 18th Annual Meeting, Toronto, 13–18 November 1988     

Neonatal desipramine or zimeldine treatment causes long-lasting changes in brain monoaminergic systems and alcohol related behavior in rats

To study the relationship between neonatal antidepressant administration, active (REM) sleep and adult alcohol-related behavior, rat pups were treated daily with 5 mg/kg despramine (DMI) or 25 mg/kg zimeldine SC from the 6th to the 19th postnatal days. Movement sensitive mattress (SCSB) measurements showed that zimeldine treatment suppressed active sleep throughout the whole treatment period, but DMI was more effective during the first 8 days than during the last treatment days. At the age of 70 days, the zimeldine-treated rats expressed a selective increase of some components of activity in the open field test, and the DMI rats had a higher defecation score compared to the controls. Furthermore, the zimeldine-rats responded with a decrease in ambulation in the open field to an alcohol dose which generally stimulates locomotion in rats. At the age of 3 months the DMI and zimeldine rats showed increased voluntary intake of 10% (v/v) alcohol. Measurement of brain monoamines revealed that the neonatal treatment with DMI or zimeldine interfered with the normal development and function of the monoamine neuronal systems: the concentrations of noradrenaline, dopamine and 5-hydroxytryptamine (5-HT), and their metabolites were altered in several brain regions. The results thus suggest that neonatal treatment with DMI or zimeldine suppresses active sleep and has an influence on later alcohol-related behavior, possibly due to a long-lasting defect in brain monoaminergic transmission.     

Auditory Brainstem Evoked Response in Juvenile Rats Fed Rat Milk Formulas with High Docosahexaenoic Acid

Abstract

Previous studies found that juvenile offspring of rats fed high docosahexaenoic acid (DHA; 22:6n-3) diets through gestation and lactation had longer auditory brainstem-evoked response (ABR) accompanied by higher 22:6n-3 and lower arachidonic acid (ARA; 20:4n-6) in brain. In the present study, ABR was assessed in juvenile rats fed high-DHA diets only postnatally.

Methods: Rat pups were fed rat milk formulas with varying amounts of DHA and ARA to 19 days of age followed by diets with the corresponding fatty acids. The high-DHA group was fed 2.3% of fatty acids as DHA, the DHA+ARA group was fed DHA and ARA at 0.6 and 0.4% of fatty acids, levels similar to those in some infant formulas, and the unsupplemented group was fed no DHA or ARA. ABR and fatty acid and monoamine levels in brain were measured on postnatal days 26-28. Statistical analyses were measured by ANOVA.

Results: ARA and DHA levels in brain increased with supplementation. ABR was shorter in the high-DHA group than the DHA+ARA group and not different from the unsupplemented or dam-reared suckling group. Norepinephrine levels in the inferior colliculus were lower in the high-DHA group than the DHA+ARA group and higher in all formula groups compared to the dam-reared group.

Conclusion: In contrast to the longer ABR in juvenile offspring of rats fed high-DHA through gestation and lactation, ABR was shorter in juvenile rats fed high-DHA diets only after birth than rats fed ARA+DHA. Further studies are needed to understand the relationship between dietary DHA, norepinephrine, and auditory system development over a range of DHA intakes and discrete periods of development.     

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