Effects of Suanzaorentang on behavior changes and central monoamines

Previously, it was found that the ancient Chinese remedy of Suanzaorentang could be a promising anxiolytic drug (Chen and Hsieh, 1985a, Chen and Hsieh, 1985b). To understand the mechanism of the action of Suanzaorentang, the effects of Suanzaorentang on behavior changes and central monoamines and their metabolites were studied in rats. It was found that Suanzaorentang significantly (1) prolonged the period from the onset of clonic to tonic convulsions induced by pentylenetetrazol or picrotoxin, (2) prolonged the sleep duration induced by hexobarbital, (3) reduced locomotor activity, (4) enhanced the hypomotility induced by alpha-MT, (5) reduced the locomotor stimulation produced by levodopa plus benserazide, and (6) reduced central HVA, VMA, and 5-HIAA, but had no significant effects on central DA, NA, and 5-HT. These facts implied that Suanzaorentang decreased the turnover rate of central monoamines and central catecholaminergic activity.     

Fish oil ameliorates sickness behavior induced by lipopolysaccharide in aged mice through the modulation of kynurenine pathway

Sickness behavior is an expression of a central motivational state triggered by activation of the immune system, being considered a strategy of the organism to fight infection. Sickness behavior is induced by peripheral administration of lipopolysaccharide (LPS). LPS can increase the levels of proinflammatory cytokines, which induce the activation of the kynurenine pathway (KP) and behavioral alterations. Previous studies have shown that omega-3 (n-3) polyunsaturated fatty acid (PUFA) has anti-inflammatory properties. Because of this, the purpose of the present study was to evaluate the protective effect of fish oil (FO) supplementation against LPS-induced sickness behavior in aged mice with respect to anhedonia, locomotor activity and body weight. Moreover, we evaluated the ability of FO treatment on the regulation of neuroinflammation (levels of interleukin-1β, interleukin-6, tumor factor necrosis-α and interferon-γ), KP biomarkers (levels of tryptophan, kynurenine, kynurenic acid, 3-hydroxykynurenine and quinolinic acid and activities of indoleamine-2,3-dioxygenase, kynurenine monooxygenase and kynurenine aminotransferase) and serotonergic system (levels of serotonin and 5-hydroxyindoleactic acid) in the hippocampus, striatum and prefrontal cortex of LPS-treated mice. We found that FO prevented the LPS-mediated body weight loss, anhedonic behavior, reduction of locomotor activity, up-regulation of the proinflammatory cytokines and serotoninergic alterations. We also found that FO was effective in modulating the KP biomarkers, inhibiting or attenuating KP dysregulation induced by LPS. Together, our results indicated that FO may have beneficial effects on LPS induced sickness-behavior in aged mice either by modulating central inflammation, KP and serotonergic signaling (indirectly effect) or by fatty acids incorporation into neuronal membranes (direct effect).     

Effect of brain serotonin on the arterial pressure and plasma renin in normal and hypertensive rats]

The effects of changes in brain serotonin content after injections of p-chlorophenylalanine (p-CPA), L-5-hydroxytryptophan (L-5HTP) and 5-6-dihydroxytryptamine (5-6DHT) on the mean arterial pressure (MAP), plasma renin activity (PRA) and peripheral levels of atrial natriuretic peptide (ANP) have been studied in normal and hypertensive (2K:1C model) male Wistar rats. The p-CPA (250 mg/kg) and L-5HTP (200 mg/kg) were injected i.p., while 5-6 DHT (15 micrograms/animal in 10 mu/animal vehicle) was injected into lateral brain ventricles. The effects were studied 24 h after the p-CPA injection, 2 h after L-5HTP and 10 or 20 days after 5-6DHT administration. The fall in brain serotonin produced by p-CPA and 5-6DHT did not modify the MAP values in the normal and hypertensive rat model, whereas the increase induced after L-5HTP injection only caused a slight decrease in arterial pressure in normotensive animals. The ARP experimented remarkable rises in the normal and hypertensive rats, these values increasing after L-5HTP and falling after p-CPA and 5-6 DHT injections. Similar changes are detected in the normal group after administration of these substances related to serotoninergic brain activity. The ANP levels rose after renal artery constriction, and they are not affected by the above mentioned substances. Only p-CPA and 5-6DHT reduced a low decrease in the ANP levels 10 days after their administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intrastriatal Injection of 5,7-Dihydroxytryptamine Decreased 5-HT Levels in the Striatum and Suppressed Locomotor Activity in C57BL/6 Mice

Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 5,7-dihydroxytryptamine (5,7-DHT) on striatal levels of dopamine (DA), 5-hydroxytryptamine (5-HT), and their metabolites, as well as on locomotor activity were investigated in C57BL/6 mice. The results showed that MPTP significantly increased locomotor activity and decreased striatal DA levels. However, injection of the serotonergic neurotoxin 5,7-DHT in the striatum, either alone or following high doses of MPTP, significantly decreased locomotor activity, and concomitantly decreased striatal levels of 5-HT and 5-HIAA. This study suggests that the increased locomotor activity may be due to increased striatal serotonergic activity which overcompensates for the DA deficiency. The locomotor hypoactivity, induced by 5,7-DHT, might be due to the decreased striatal levels of 5-HT and 5-HIAA.     

n-3 polyunsaturated fatty acid supplementation reverses stress-induced modifications on brain monoamine levels in mice

The aim of this study was to examine the effects of supplementation with n-3 polyunsaturated fatty acids (PUFAs) on stress responses in mice subjected to an unpredictable chronic mild stress (UCMS) procedure. Stress-induced modifications in coat and aggressiveness were evaluated, and phospholipid PUFA profiles and monoamine levels were analyzed in the frontal cortex, hippocampus, and striatum. The results showed that repeated exposure to mild stressors induced degradation in the physical state of the coat, lowered body weight gain, and increased aggressiveness, without any effect of n-3 PUFA supplementation. The UCMS induced a significant decrease in the levels of norepinephrine in the frontal cortex and striatum, and a nonsignificant decrease in the hippocampus. The tissue levels of serotonin (5-HT) were 40% to 65% decreased in the three brain regions studied. Interestingly, the n-3 PUFA supplementation reversed this stress-induced reduction in 5-HT levels. These findings showed that supplementation in n-3 long-chain PUFAs might reverse certain effects of UCMS in cerebral structures involved in stress-related behaviors.     

Effects of chronic mild stress on the oxidative parameters in the rat brain

Major depression is characterized for symptoms at the psychological, behavioral and physiological levels. The chronic mild stress model has been used as an animal model of depression. The consumption of sweet food, locomotor activity, body weight, lipid and protein oxidation levels and superoxide dismutase and catalase activities in the rat hippocampus, prefrontal cortex and cortex were assessed in rats exposed to chronic mild stress. Our findings demonstrated a decrease on sweet food intake, no effect on locomotor activity, lack of body weight gain, increase in protein (prefrontal, hippocampus, striatum and cortex) and lipidic peroxidation (cerebellum and striatum), and an increase in catalase (cerebellum, hippocampus, striatum, cortex) and a decrease in superoxide dismutase activity (prefrontal, hippocampus, striatum and cortex) in stressed rats. In conclusion, our results support the idea that stress produces oxidants and an imbalance between superoxide dismutase and catalase activities that contributes to stress-related diseases, such as depression.     

Subchronic Oral Administration of Benzo[a]pyrene Impairs Motor and Cognitive Behavior and Modulates S100B Levels and MAPKs in Rats

Benzo[a]pyrene (BaP) is an environmental contaminant produced during incomplete combustion of organic material that is well known as a mutagenic and carcinogenic toxin. There are few studies addressing the molecular and cellular basis of behavioural alterations related to BaP exposure. The aim of this study was to evaluate the effect of subchronic oral administration of BaP on behavioral and neurochemical parameters. Wistar male rats received BaP (2 mg/kg) or corn oil (control), once a day for 28 days (n = 12/group). Spontaneous locomotor activity and short- and long-term memories were evaluated. Glial fibrillary acid protein and S100B content in the hippocampus, serum and CSF were measured using ELISA and total and phosphorylated forms of mitogen activated protein kinases (MAPKs) named extracellular signal-regulated kinases 1 and 2, p38^MAPK and c-Jun amino-terminal kinases 1 and 2, in the hippocampus, were evaluated by western blotting. BaP induced a significant increase on locomotor activity and a decrease in short-term memory. S100B content was increased significantly in cerebrospinal fluid. BaP induced a decrease on ERK2 phosphorylation in the hippocampus. Thus, BaP subchronic treatment induces an astroglial response and impairs both motor and cognitive behavior, with parallel inhibition of ERK2, a signaling enzyme involved in the hippocampal neuroplasticity. All these effects suggest that BaP neurotoxicity is a concern for environmental pollution.     

Differential Response of Central Dopaminergic System in Acute and Chronic Unpredictable Stress Models in Rats

We aimed to evaluate the response of dopaminergic system in acute stress (AS) and chronic unpredictable stress (CUS) by measuring dopamine (DA) levels, its receptor densities in the frontal cortex, striatum, hippocampus, amygdala and orbito-frontal cortex regions of rat brain, and investigated the corresponding behavioral locomotor changes. Involvement of D₁ receptor was also examined during AS and CUS using A 68930, a D₁ selective agonist. Rats were exposed to AS (single immobilization for 150 min) and CUS (two different stressors for 7 days). AS significantly decreased the DA levels in the striatum and hippocampus, and A 68930 pretreatment significantly reverted these changes. However, in the frontal cortex significantly increased DA levels were remain unchanged following A 68930. CUS led to a decrease of DA levels in the frontal cortex, striatum and hippocampus, which were normalized by A 68930. Saturation radioligand binding assays revealed a significant decrease in the number of D₁-like receptors in the frontal cortex during CUS, which were further decreased by A 68930 pretreatment. However, in the striatum and hippocampus, A 68930 pretreatment reduced the CUS induced increase in the number of D₁-like receptors. No significant changes were observed in the amygdala and orbito-frontal cortex during AS and CUS, while D₂-like receptors were unchanged in all the brain regions studied. Locomotor activity was significantly decreased in both the stress models, A 68930 pretreatment significantly increased stereotypic counts and horizontal activity. Thus, present investigation provide insights into the differential regional response of dopaminergic system during AS and CUS. Further, neurochemical and behavioral effects of D₁ agonist pretreatment suggest specific modulatory role of D₁ receptor under such stressful episodes.     

Rosmarinic acid prevents lipid peroxidation and increase in acetylcholinesterase activity in brain of streptozotocin‐induced diabetic rats

We investigated the efficacy of rosmarinic acid (RA) in preventing lipid peroxidation and increased activity of acetylcholinesterase (AChE) in the brain of streptozotocin‐induced diabetic rats. The animals were divided into six groups (n = 8): control, ethanol, RA 10 mg/kg, diabetic, diabetic/ethanol and diabetic/RA 10 mg/kg. After 21 days of treatment with RA, the cerebral structures (striatum, cortex and hippocampus) were removed for experimental assays. The results demonstrated that the treatment with RA (10 mg/kg) significantly reduced the level of lipid peroxidation in hippocampus (28%), cortex (38%) and striatum (47%) of diabetic rats when compared with the control. In addition, it was found that hyperglycaemia caused significant increased in the activity of AChE in hippocampus (58%), cortex (46%) and striatum (30%) in comparison with the control. On the other hand, the treatment with RA reversed this effect to the level of control after 3 weeks. In conclusion, the present findings showed that treatment with RA prevents the lipid peroxidation and consequently the increase in AChE activity in diabetic rats, demonstrating that this compound can modulate cholinergic neurotransmission and prevent damage oxidative in brain in the diabetic state. Thus, we can suggest that RA could be a promising compound in the complementary therapy in diabetes. Copyright © 2013 John Wiley & Sons, Ltd.     

Effects of Two Convulsant β-Carboline Derivatives, DMCM and β-CCM, on Regional Neurotransmitter Amino Acid Levels and on In Vitro D-[3H]Aspartate Release in Rodents

Clonic seizures were induced in Swiss or DBA/2 mice by methyl-6-7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), 0.048 mmol/kg i.p., or by methyl-beta-carboline-3-carboxylate (beta-CCM), 0.044 mmol/kg i.p. Measurement of regional brain (cortex, hippocampus, striatum, and cerebellum) amino acid levels after 15 min of seizure activity showed increases in gamma-aminobutyric acid (GABA) (in all regions after beta-CCM, and in cortex and hippocampus after DMCM), and an increase in glycine in the striatum after beta-CCM. Aspartate levels fell (in cortex and hippocampus) after DMCM, but were unchanged in all regions after beta-CCM. Glutamate levels fell in cortex after beta-CCM and in striatum after DMCM. Pretreatment with the excitatory amino acid receptor antagonist, 2-amino-7-phosphonoheptanoic acid, 0.5 mmol/kg i.p., 45 min prior to the beta-carboline, significantly increased the ED50 for DMCM-induced clonic seizures (4.68 mumol/kg vs. 9.39 mumol/kg). Similar pretreatment did not significantly alter the ED50 for beta-CCM (4.22 mumol/kg vs. 6.6 mumol/kg). Pretreatment with 2-amino-7-phosphonoheptanoic acid, 1.0 mmol/kg, blocked the increase in GABA content produced by DMCM but not the fall in cortical aspartate content. Potassium-induced release of preloaded D-[3H]aspartate from rat cortical or hippocampal minislices was enhanced in the presence of DMCM (100 microM). In contrast, stimulated release of D-[3H]aspartate (from cortex or hippocampus) was not altered in the presence of beta-CCM (100 microM). Although DMCM and beta-CCM are both considered to induce convulsion by acting at the GABA--benzodiazepine receptor complex, the convulsions differ in several pharmacological and biochemical respects. It is suggested that enhanced release of excitatory amino acid neurotransmitters plays a more important role in seizures induced by DMCM.     

Amperozide, a Novel Antipsychotic Drug, Inhibits the Ability of d-Amphetamine to Increase Dopamine Release In Vivo in Rat Striatum and Nucleus Accumbens

The in vivo effects of amperozide, a novel atypical antipsychotic drug, on the release of dopamine (DA) and the output of its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), were investigated in the striatum and the nucleus accumbens of awake, freely moving rats using microdialysis. Amperozide (2-10 mg/kg, s.c.) significantly increased extracellular levels of DA in both the striatum and nucleus accumbens in a dose-dependent manner. It had a similar but lesser effect on extracellular DOPAC levels in both regions. d-Amphetamine (2 mg/kg, s.c.) alone produced a very large (43-fold) increase in DA release, together with a 70% decrease in DOPAC levels in both the striatum and the nucleus accumbens. Amperozide (1-5 mg/kg, s.c.) 30 min before d-amphetamine (2 mg/kg) dose-dependently attenuated d-amphetamine-induced DA release but had no effect on the d-amphetamine-induced decrease in extracellular DOPAC levels in both regions. The effect of amperozide on d-amphetamine-induced DA release in the nucleus accumbens may explain the inhibitory effect of amperozide on amphetamine-induced locomotor activity. However, the failure of amperozide to block amphetamine-induced stereotypy, despite marked inhibition of striatal DA release, suggests the need to reexamine the importance of striatal DA for amphetamine-induced stereotypy.     

Fluoxetine potentiates the effects of corticotropin-releasing factor on locomotor activity and serotonergic systems in the roughskin newt, Taricha granulosa

The anxiety- and stress-related neuropeptide corticotropin-releasing factor (CRF) elicits behavioral changes in vertebrates including increases in behavioral arousal and locomotor activity. Intracerebroventricular injections of CRF in an amphibian, the roughskin newt (Taricha granulosa), induces rapid increases in locomotor activity in both intact and hypophysectomized animals. We hypothesized that this CRF-induced increase in locomotor activity involves a central effect of CRF on serotonergic neurons, based on known stimulatory actions of serotonin (5-hydroxytryptamine, 5-HT) on spinal motor neurons and the central pattern generator for locomotor activity in vertebrates. In Experiment 1, we found that neither intracerebroventricular injections of low doses of CRF (25 ng) nor the selective serotonin reuptake inhibitor fluoxetine (10, 100 ng), by themselves, altered locomotor activity. In contrast, newts treated concurrently with CRF and fluoxetine responded with marked increases in locomotor activity. In Experiment 2, we found that increases in locomotor activity following co-administration of CRF (25 ng) and fluoxetine (100 ng) were associated with decreased 5-HT concentrations in a number of forebrain structures involved in regulation of emotional behavior and emotional states, including the ventral striatum, amygdala pars lateralis, and dorsal hypothalamus, measured 37 min after treatment. These results are consistent with the hypothesis that CRF stimulates locomotor activity through activation of serotonergic systems.     

The neurosteroid dehydroepiandrosterone sulfate,but not androsterone,enhances the antidepressant effect of cocaine examined in the forced swim test — Possible role of serotonergic neurotransmission

One of the mechanisms of cocaine's actions in the central nervous system is its antidepressant action. This effect might be responsible for increased usage of the drug by individuals with mood disorders. Higher endogenous levels of the excitatory neurosteroid dehydroepiandrosterone sulfate (DHEAS) were reported to correlate with successful abstinence from cocaine use in addicts, but a clinical trial showed that supplementation with a high dose of DHEA increased cocaine usage instead. Such ambiguous effects of DHEA(S) could potentially be linked to its influence on the antidepressant effect of cocaine. In this study we tested DHEAS and its metabolite, androsterone, for interactions with cocaine in animal model of depression (forced swim test) and examined the effects of both steroids and cocaine on serotoninergic neurotransmission. All substances were also tested for influence on locomotor activity. A cocaine dose of 5 mg/kg, which had no significant effect on locomotor activity, was chosen for the forced swim test. Neither DHEAS nor androsterone showed any antidepressant action in this test, while cocaine manifested a clear antidepressant effect. Androsterone slightly reduced the antidepressant influence of cocaine while DHEAS markedly, dose-dependently enhanced it. Such an effect might be caused by the influence of DHEAS on serotonin neurotransmission, as this steroid decreased serotonin concentration and turnover in the striatum. When DHEAS and cocaine were administered together, the levels of serotonin in the striatum and hippocampus remained unchanged. This phenomenon may explain the additive antidepressant action of DHEAS and cocaine and why co-administration of DHEAS and cocaine increases drug use.     

Omega-3 Fatty Acids and Mood Stabilizers Alter Behavioural and Energy Metabolism Parameters in Animals Subjected to an Animal Model of Mania Induced by Fenproporex

Studies have shown that changes in energy metabolism are involved in the pathophysiology of bipolar disorder (BD). It was suggested that omega-3 (ω3) fatty acids have beneficial properties in the central nervous system and that this fatty acid plays an important role in energy metabolism. Therefore, the study aimed to evaluate the effect of ω3 fatty acids alone and in combination with lithium (Li) or valproate (VPA) on behaviour and parameters of energy metabolism in an animal model of mania induced by fenproporex. Our results showed that co-administration of ω3 fatty acids and Li was able to prevent and reverse the increase in locomotor and exploratory activity induced by fenproporex. The combination of ω3 fatty acids with VPA was only able to prevent the fenproporex-induced hyperactivity. For the energy metabolism parameters, our results showed that the administration of Fen for the reversal or prevention protocol inhibited the activities of succinate dehydrogenase, complex II and complex IV in the hippocampus. However, hippocampal creatine kinase (CK) activity was decreased only for the reversal protocol. The ω3 fatty acids, alone and in combination with VPA or Li, prevented and reversed the decrease in complex II, IV and succinate dehydrogenase activity, whereas the decrease in CK activity was only reversed after the co-administration of ω3 fatty acids and VPA. In conclusion, our results showed that the ω3 fatty acids combined with VPA or Li were able to prevent and reverse manic-like hyperactivity and the inhibition of energy metabolism in the hippocampus, suggesting that ω3 fatty acids may play an important role in the modulation of behavioural parameters and energy metabolism.     

Changes in Monoamine Turnover in the Brain of Cachectic Mice Bearing Colon-26 Tumor Cells

Abstract: Patients with cancer cachexia often suffer from psychiatric disorders. In the present study, we investigated the changes in monoaminergic activities in the brain in tumor-bearing mice with reference to the development of cachexia. Two clones, clone-5 (noncachectic clone) and clone-20 (cachectic clone), derived from the murine Colon-26 adenocarcinoma cell line (Nippon Roche Research Center), were inoculated subcutaneously at 1 × 10⁶ cells/0.2 ml into the right lower back of BALB/c mice. In clone-20 mice, body weight and locomotor activity decreased significantly 10–15 days after tumor inoculation. The levels of noradrenaline, dopamine, and 3,4-dihydroxyphenylacetic acid showed no significant change among the three groups. The noradrenaline turnover rate in clone-20 mice was increased in cerebral cortex, hypothalamus, and midbrain. The 5-hydroxytryptamine turnover rate in clone-20 mice was increased in hippocampus, cerebral cortex, midbrain, and pons-medulla oblongata. In contrast, the dopamine turnover rate in clone-20 mice was decreased markedly in hippocampus, cerebral cortex, striatum, hypothalamus, and cerebellum. There was no significant change in amine turnover between control and clone-5 mice except for dopamine in hippocampus, cerebral cortex, and striatum and 5-hydroxytryptamine in striatum. No significant change in the levels of amino acids in the brain was observed among the three groups of mice. It is concluded that some of the psychiatric disorders from which cancer cachectic patients suffer might be ascribable to changes in monoaminergic activities in the brain.     

不同甲状腺功能状态对成年大鼠中枢5—HT1A受体密度的影响

用三碘甲状腺原氨酸(T_3)和丙基硫氧嘧啶(PTU)灌胃分别制成大鼠的甲状腺机能亢进症(简称甲亢)和甲状腺机能低下症(简称甲低)模型。灌药后甲亢组心率、氧耗量、肛温以及血浆T_3浓度较对照组显著增高;在甲低组则均降低。氚标8-羟基-2-(二正丙氨基)-四氢化萘([~3H]8-OH-DPAT)的受体结合实验显示甲亢组海马的5-HT_(1A)受体结合数较对照组显著增加,皮层减低,下丘脑、脑干和纹状体无显著变化。Scatchard分析示甲文组[~3H]8-OH-DPAT在海马中的最大结合容量(B_(max))增加,皮层减低,K_D无变化。甲低组在上述脑区均未见显著变化。上述5-HT_(1A)受体的变化是否与甲亢并发精神神经障碍的机制有关,尚待进一步研究。     

Modifications in muscarinic, dopaminergic and serotonergic receptors concentrations in the hippocampus and striatum of epileptic rats

The present study was undertaken in order to investigate the muscarinic (M(1)), dopaminergic (D(1) and D(2)) and serotonergic (5-HT(2)) receptors densities in hippocampus and striatum of Wistar rats after status epilepticus (SE) induced by pilocarpine. The control group was treated with 0.9% saline. An other group of rats received pilocarpine (400 mg/kg, s.c.) and both groups were sacrificed 1 h after treatment. The results have shown that pilocarpine administration and resulting SE produced a downregulation of M(1) receptor in hippocampus (41%) and striatum (51%) and an increase in the dissociation constant (K(d)) values in striatum (42%) alone. In both areas the 5-HT(2) receptor density remained unaltered, but a reduction (50%) and an increase (15%) in the K(d) values were detected in striatum and hippocampus, respectively. D(1) and D(2) receptor densities in hippocampus and striatum remained unaltered meanwhile K(d) values for D(1) receptor declined significantly, 33% in hippocampus and 26% in striatum. Similarly, K(d) values for D(2) decreased 55% in hippocampus and 52% in striatum. From the preceding results, it is clear that there is a possible relation between alterations in muscarinic receptor density and others systems studied as well as they suggest that changes in dissociation constant can be responsible for the establishment of pilocarpine-induced SE by altering the affinity of neurotransmitters such as acetylcholine, dopamine and serotonine.     

Effect of Theanine,r-Glutamylethylamide,on Brain Monoamines and Striatal Dopamine Release in Conscious Rats

Theanine, r-glutamylethylamide, is one of the major components of amino acids in Japanese green tea. Effect of theanine on brain amino acids and monoamines, and the striatal release of dopamine (DA) was investigated. Determination of amino acids in the brain after the intragastric administration of theanine showed that theanine was incorporated into brain through blood-brain barrier via leucine-preferring transport system. The concentrations of norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5HIAA) in the brain regions were unaffected by the theanine administration except in striatum. Theanine administration caused significant increases in serotonin and/or DA concentrations in the brain, especially in striatum, hypothalamus and hippocampus. Direct administration of theanine into brain striatum by microinjection caused a significant increase of DA release in a dose-dependent manner. Microdialysis of brain with calcium-free Ringer buffer attenuated the theanine-induced DA release. Pretreatment with the Ringer buffer containing an antagonist of non-NMDA (N-methyl-D-aspartate) glutamate receptor, MK-801, for 1 hr did not change the significant increase of DA release induced by theanine. However, in the case of pretreatment with AP-5, (±)-2-amino-5-phosphonopentanoic acid; antagonist of NMDA glutamate receptor, the theanine-induced DA release from striatum was significantly inhibited. These results suggest that theanine might affect the metabolism and/or the release of some neurotransmitters in the brain, such as DA.     

花粉制剂对脑衰老动物各脑区的SOD和NO水平的影响

采用 D-半乳糖建立脑衰老动物模型 ,观察服用花粉制剂前后对脑衰老模型动物不同脑区组织中超氧化物歧化酶 ( SOD)活性、一氧化氮 ( NO)水平的影响。结果表明花粉制剂能明显升高脑衰老动物某些脑区 SOD活性和降低脑衰老动物某些脑区 NO水平。研究结果提示花粉制剂具有延缓衰老和增强记忆力等作用 ,其机制可能与其促进自由基的清除及减少 NO释放有关。     

A comparison of the locomotor effects induced by centrally injected TRH and TRH analogues

Thyrotrophin-releasing hormone (TRH) and its stable analogues CG3509 and RX77368 were injected directly into the nucleus accumbens, septum and striatum of the rat and locomotor activity was recorded. TRH (5-20 micrograms) caused a dose-dependent increase in locomotor activity when injected into the nucleus accumbens. TRH (20 micrograms) also increased locomotor activity after administration into the septum but not when put into the striatum. Both the TRH analogues (0.1 and 1.0 microgram) produced closely related increases in activity when injected into either the nucleus accumbens or septum but CG3509 was more potent with a longer lasting effect. Also, in contrast with TRH (20 micrograms), both TRH analogues stimulated locomotor activity when injected into the striatum at a dose of 1 microgram but the effect was less marked and delayed in onset compared to the nucleus accumbens and septum response. Dopamine (100 micrograms) injected into the accumbens or septum also produced significant increases in locomotor activity. The locomotor effects of the peptides are discussed in relation to a possible dopamine-mediated mechanism which contrasts with the actions of TRH and the analogues on barbiturate anaesthesia.