Escapable and inescapable stress differentially and selectively alter extracellular levels of 5-HT in the ventral hippocampus and dorsal periaqueductal gray of the rat

The effects of escapable and yoked inescapable electric tailshocks on extracellular levels of serotonin (5-HT) in the ventral hippocampus and dorsal periaqueductal gray (dPAG) were measured by in vivo microdialysis. Inescapable, but not escapable shock increased extracellular 5-HT in the ventral hippocampus relative to restrained controls. Basal levels of 5-HT were elevated 24 h after inescapable shock, and previously inescapably shocked subjects exhibited an exaggerated 5-HT response to 2 brief footshocks. In contrast, escapable, but not inescapable shock, increased extracellular 5-HT in the dPAG, increased basal 5-HT in the dPAG 24 h later, and led to an enhanced 5-HT response to subsequent brief footshock.     

Endogenous serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) levels in large regions and in discrete brain areas of C57BL and BALBc mice at three times of the day

The serotoninergic system has been analysed in the brainstem and the forebrain of adult C57BL and BALBc mice. Endogenous 5-HT and 5-HIAA levels have also been measured in the different raphe nuclei and in the caudate nucleus and the hippocampus of these strains, using the micropunch technique and the radioenzymatic method (for 5-HT) and a new radioimmunoassay (for 5-HIAA). This investigation was performed at three times of the day: 9:00 hr; 14:00 hr; 20:00 hr to underline the differences between the strains. Most of the time, higher 5-HT and 5-HIAA levels are found in the brainstem and the raphe nuclei of the BALBc strain compared to C57BL. In the forebrain the differences are reversed, except in the caudate nucleus and the hippocampus where the levels of 5-HT are identical in the two strains. Moreover the 5-HIAA/5-HT ratio shows a higher turn-over of the amine in the C57BL strain.     

Tryptophan increases extracellular serotonin in the lateral hypothalamus of food-deprived rats

Although it is well established that increases in tryptophan availability can increase brain serotonin synthesis, the effect of tryptophan loads on serotonin release is not as clear. We have used in vivo microdialysis in order to monitor extracellular serotonin in the lateral hypothalamus to examine this issue. Tryptophan methyl ester (100 mg/kg IP) was administered to ad lib-fed and 48-h food-deprived rats. The results suggest that a peripheral tryptophan load can elevate extracellular serotonin in food-deprived subjects more effectively than in food-replete subjects.     

人参皂甙Rd对颞叶癫大鼠学习记忆能力及海马5-HT表达的影响

目的研究人参皂甙Rd对氯化锂-匹罗卡品点燃颞叶癫(temporal lobe epilepsy,TLE)大鼠学习记忆能力及海马5-HT表达的干预作用。方法建立氯化锂-匹罗卡品点燃颞叶癫大鼠模型,将30只造模成功的颞叶癫大鼠随机分为TLE组(生理盐水10ml/kg腹腔注射,15只)及GSRd干预组(人参皂甙Rd2mg/kg腹腔注射,15只),另选15只大鼠作为正常对照组;采用Morris水迷宫及免疫组化染色分别检测各组大鼠学习记忆能力及海马5-HT表达水平。结果与正常对照组比较,TLE组大鼠学习记忆能力下降,海马5-HT表达明显减少(P0.05);与TLE组比较,GSRd干预组可显著提高大鼠学习记忆能力及海马5-HT的表达水平(P0.05)。结论人参皂甙Rd可能通过增加海马5-HT的表达来提高颞叶癫大鼠学习记忆能力。     

Escapable and inescapable stress differentially alter extracellular levels of 5-HT in the basolateral amygdala of the rat

The effects of escapable and yoked inescapable electric tailshocks on extracellular levels of serotonin (5-HT) in the basolateral amygdala were measured by in vivo microdialysis. Inescapable, but not escapable, shock increased extracellular 5-HT in the amygdala relative to restrained controls. Basal levels of 5-HT were elevated 24 h after inescapable shock, and previously inescapably shocked subjects exhibited an exaggerated 5-HT response to two brief footshocks. Levels of extracellular 5-HIAA did not follow any particular pattern and were not correlated with the changes in 5-HT.     

Exposure to inescapable but not escapable shock increases extracellular levels of 5-HT in the dorsal raphe nucleus of the rat

The effects of escapable and yoked inescapable electric tailshocks on extracellular levels of serotonin (5-HT) in the dorsal raphe nucleus were measured by in vivo microdialysis. In comparison to either control rats or to their own preshock baseline, rats exposed to inescapable shock showed an increase in extracellular 5-HT within 25 min of shock initiation, and 5-HT levels continued to rise during the remainder of the shock session. Rats that were exposed to comparable shock treatment, but that were given the opportunity to escape, did not show an increase in 5-HT. Rats that were restrained but not shocked also did not show an increase in 5-HT. These results add further support to suggestions that serotonergic changes occur in the dorsal raphe nucleus during inescapable shock and that such changes may contribute to the behavioral effects of inescapable shock.     

Chronic treatment with antidepressant drugs reversibly alters NMDA mediated regulation of extracellular 5-HT in rat frontal cortex

Treatment of depression is largely based upon the monoamine theory of the illness. However, current therapies are only efficacious in 70-80% of patients indicating that other factors are involved. One mechanism could involve glutamatergic NMDA receptors since NMDA receptor antagonists have antidepressant like properties in paradigms of the illness. We have observed that the tricyclic clomipramine given chronically decreases NMDA mediated alterations in extracellular 5-hydroxytryptamine (5-HT). We have now studied whether this observation extends to other antidepressant drugs (AD's), reboxetine and parxoetine and also if the phenomenon is reversible after treatment is discontinued. To do this we have studied cortical extracellular 5-HT in rats using microdialysis. Acutely, none of the AD's altered extracellular 5-HT, while 100 microM NMDA infusion evoked an increase. All three AD's increased extracellular 5-HT after 14 days of treatment, however, at the same time the effects of NMDA on extracellular 5-HT were abolished. In vehicle only treated rats NMDA infusion still evoked a significant increase in extracellular 5-HT. This situation was unchanged after 3 days of drug washout with 5-HT levels remaining high and no response to NMDA infusion occurred. After 14 days of antidepressant washout, however, extracellular 5-HT levels in all three AD drug groups were around basal values. In these groups NMDA infusion now evoked an increase in extracellular 5-HT comparable to that seen in vehicle treated rats. If a reduction in NMDA receptor activity plays a role in AD drug action these observations could be of possible therapeutic significance.     

Lithium addition in antidepressant-resistant depression: effects on platelet 5-HT, plasma 5-HT and plasma 5-HIAA concentration

The efficacy of the addition of lithium to an established course of antidepressant treatment can be explained by a synergistic effect of the two drugs on central 5-HT neurotransmission. In the present study we investigated the effect of lithium addition on the 5-HT concentration in plasma and platelets and the concentration of 5-HIAA. Thirty-nine depressed inpatients who fulfilled the DSM-IV criteria for major depressive disorder and who did not respond to monotherapy with either imipramine or fluvoxamine participated in this study. Concentration of 5-HT in both plasma and platelets did not change significantly during lithium addition. The 5-HT ratio (plasma concentration/platelet concentration) shows a small non-significant increase after 3 weeks lithium addition. The mean concentration of 5-HIAA shows a significant increase during lithium addition; with no difference between the imipramine and the fluvoxamine sample. The increments in 5-HIAA concentration during lithium addition are indicative of an increased 5-HT turnover.     

Wheel running alters serotonin (5-HT) transporter, 5-HT1A, 5-HT1B, and alpha 1b-adrenergic receptor mRNA in the rat raphe nuclei.

BACKGROUND: Altered serotonergic (5-HT) neurotransmission is implicated in the antidepressant and anxiolytic properties of physical activity. In the current study, we investigated whether physical activity alters factors involved in the regulation of central 5-HT neural activity. METHODS: In situ hybridization was used to quantify levels of 5-HT transporter (5-HTT), 5-HT(1A), 5-HT(1B), and alpha(1b)-adrenergic receptor (alpha(1b) ADR) messenger ribonucleic acids (mRNAs) in the dorsal (DRN) and median raphe (MR) nuclei of male Fischer rats after either sedentary housing or 3 days, 3 weeks, or 6 weeks of wheel running. RESULTS: Wheel running produced a rapid and lasting reduction of 5-HT(1B) mRNA in the ventral DRN. Three weeks of wheel running decreased 5-HTT mRNA in the DRN and MR and increased alpha(1b) ADR mRNA in the DRN. After 6 weeks of wheel running, 5-HTT mRNA remained reduced, but alpha(1b) ADR mRNA returned to sedentary levels. Serotonin(1A) mRNA was increased in the MR and certain DRN subregions after 6 weeks only. CONCLUSIONS: Data suggest that the central 5-HT system is sensitive to wheel running in a time-dependent manner. The observed changes in mRNA regulation in a subset of raphe nuclei might contribute to the stress resistance produced by wheel running and the antidepressant and anxiolytic effects of physical activity.     

Effect of extracellular long-time microperfusion of high concentrations of glutamate and glycine on picrotoxin seizure thresholds in the hippocampus of freely moving rats

The effect of high concentrations of glutamate and glycine on picrotoxin seizure thresholds was investigated by perfusion through microdialysis probes in the hippocampus of freely moving rats. Microperfusion of glutamate at concentrations up to 1 mM, produced no changes in behavior or basal EEG recordings, but microperfusion of 200 microM glutamate was sufficient to lower the picrotoxin seizure threshold down to 50% in 60% of the animals studied and produced an increase of 180+/-23% in seizure duration. Microperfusion of 1 mM glutamate reduced seizure threshold in all animals, and markedly prolonged seizure duration (230+/-30%). Microperfusion of 200 microM or 1 mM glycine lowered picrotoxin seizure thresholds down to 50% in 70% of the animals and lengthened seizure duration up to 176+/-43%. Continuous microperfusion of the antagonist for the glycine binding site in NMDA receptors 5,7-dichlorokynurenic acid (100 microM) reversed the effect of both glutamate (1 mM) and glycine (1 mM) and suppressed seizures completely in 90% of the animals. These results indicate that although neurotoxicity is not achieved by perfusing glutamate and glycine at concentrations as high as 1 mM, neuronal excitability is modified by altering extracellular glutamate and glycine concentrations, and they suggest that glutamate-induced neuronal hyperexcitability is induced through mechanisms different from excitotoxicity.     

Effects of conditioned taste aversion on extracellular serotonin in the lateral hypothalamus and hippocampus of freely moving rats

This study used microdialysis to monitor extracellular levels of 5-HT and its metabolite, 5-hydroxyindole acetic acid (5-HIAA) in the lateral hypothalamus (LH) and hippocampus of freely moving rats that had developed a CTA to a 2.5 mM saccharin solution (CS) following its pairing with illness induced by lithium chloride (US). Results showed that oral infusion of the saccharin CS significantly enhanced extracellular LH 5-HT in animals that had developed a taste aversion compared with control groups, including unconditioned (CS-no US) and pseudoconditioned (no CS-US) subjects. As an anatomical control, the hippocampus was identified based on previous research suggesting that it is not integrally involved in CTA learning or retrieval and that 5-HT in this brain site does not directly mediate feeding behavior but is closely correlated with arousal. In contrast with the results obtained in the LH, hippocampal 5-HT was not preferentially elevated in subjects in the CTA group but rather was increased to the same extend in both CTA and control groups after saccharin infusion. Moreover, the increase in LH 5-HT for the CTA group was nearly twice that observed in the hippocampus for any group. Acute administration of LiCl elevated extracellular 5-HT to similar levels in both sites, well above the changes observed following conditioning. 5-HIAA was unaffected in either brain site by oral infusion of saccharin solution or injection of LiCl.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adaption of the serotoninergic neuronal phenotype in the absence of 5-HT autoreceptors or the 5-HT transporter: involvement of BDNF and cAMP

Serotonin 5-HT1A and 5-HT1B receptors and the 5-HT transporter are key regulators of the serotoninergic neuronal phenotype. We show here that genetic deletion of any of these elements differentially regulates 5-HT neuronal number in rostral raphe cultures from E14 mice. Serotonin neuronal number was increased by almost four-fold and 1.8-fold in cultures from 5-HT1AR-/- and 5-HT1BR-/- mice, respectively. In contrast, the lack of serotonin transporter expression was associated with a 50% decrease in 5-HT neuronal number. In raphe cultures from the rat, BDNF and cAMP have been shown to up-regulate the neuronal serotoninergic phenotype through TrkB-dependent mechanisms [Rumajogee et al. (2002) J. Neurochem., 83, 1525-1528]. Similar tyrosine kinase-dependent up-regulating effects, in the absence of serotoninergic key-elements are reported here, on both 5-HT neuronal number and neurites length. However, the extents of BDNF-triggered and cAMP-triggered effects on serotoninergic neuritic length were approximately 1.5-fold higher in 5-HT1AR-/- mutants. These findings show that the up-regulatory mechanisms triggered by BDNF on serotoninergic neuronal number and neurite extension are different and that the latter are partially linked to 5-HT, probably through 5-HT1A autoreceptors. Together, these data suggest that serotonin autoreceptors, mainly 5-HT1A but also 5-HT1B, may be responsible for a tonic auto-inhibitory effect of 5-HT itself on the serotoninergic neuronal phenotype during embryonic development, particularly marked in the absence of the 5-HT transporter.     

Differential effects of restraint stress on hippocampal 5-HT metabolism and extracellular levels of 5-HT in streptozotocin-diabetic rats

Streptozotocin (STZ)-elicited diabetes reduces central serotonin (5-hydroxytryptamine, 5-HT) synthesis/metabolism, but whether this reduction leads to decreased release of 5-HT has only scarcely been investigated. We have thus analysed the impact of STZ diabetes on hippocampal extracellular 5-HT levels both under basal conditions and during restraint stress, a procedure known to stimulate hippocampal 5-HT synthesis/metabolism and release. The pretreatment with STZ (3 weeks beforehand) and the 1 h restraint session respectively decreased and increased hippocampal 5-HT metabolism, as assessed by tissue analysis of 5-HT and 5-hydroxyindoleacetic acid. On the other hand, hippocampal microdialysis revealed no difference in basal levels of extracellular 5-HT levels in (conscious) vehicle- and STZ-pretreated rats, but a differential effect of restraint. Thus, extracellular 5-HT levels increased throughout restraint (maximal increase: 194%) in vehicle-, but not in STZ-pretreated rats. In the latter rat group, plasma corticosterone levels were, however, increased, thus indicating a significant aversiveness to stress. Lastly, because anxiety-related behaviours may be affected by hippocampal serotonergic systems, resting and restrained vehicle- and STZ-pretreated rats were compared (immediately after stress) in an elevated plus-maze of anxiety. Pretreatment with STZ reduced the percent number of open arm entries and the number of closed arm entries, indicating increased anxiety and reduced locomotor activity, respectively. Restraint tended to increase anxiety-related behaviours in all rats, but this trend never reached significance. Our results confirm that gross analyses of 5-HT metabolism do not yield information on 5-HT release, and suggest that the prevalence of diabetes among patients suffering affective disorders could be related to the lack of hippocampal serotonergic response to aversive stimuli.     

Attenuated extracellular dopamine levels after stress and amphetamine in the nucleus accumbens of rats with neonatal ventral hippocampal damage

Summary. In vivo microdialysis was used to study the effects of restraint stress (30 min) and amphetamine (AMPH) (5 mg/kg, i.p.) in awake adult male rats with neonatal ventral hippocampal (VH) damage. Extracellular levels of dopamine (DA), dihydrophenylacetate (DOPAC), homovanillate (HVA) and 5-hydroxyindolacetate (5-HIAA) were measured in the nucleus accumbens (NA). There were no differences in the baseline levels of DA, DOPAC, HVA or 5-HIAA in the lesioned as compared to the sham rats. Release from restraint resulted in increased extracellular levels of DA in the sham but not in the lesioned animals. AMPH increased DA release in both sham operated and lesioned animals, but this increase was significantly attenuated in the lesioned rats. Our data suggest that this developmental lesion alters function of the dopaminergic system in response to environmental and pharmacological challenge. Received June 3, 1997; accepted August 10, 1998     

Increased binding at 5-HT1A, 5-HT1B, and 5-HT2A receptors and 5-HT transporters in diet-induced obese rats

5-Hydroxytryptamine (5-HT, serotonin), synthesized in midbrain raphe nuclei and released in various hypothalamic sites, decreases food intake but the specific 5-HT receptor subtypes involved are controversial. Here, we have studied changes in the regional density of binding to 5-HT receptors and transporters and the levels of tryptophan hydroxylase, in rats with obesity induced by feeding a palatable high-energy diet for 7 weeks. We mapped binding at 5-HT receptor subtypes and transporters using quantitative autoradiography and determined tryptophan hydroxylase protein levels by Western blotting. In diet-induced obese (DiO) rats, specific binding to 5-HT_1A receptors ([³H]8-OH-DPAT) was significantly increased in the dorsal and median raphe by 90% (P<0.01) and 132% (P<0.05), respectively, compared with chow-fed controls. 5-HT_1B receptor binding sites ([¹²⁵I]cyanopindolol) were significantly increased in the hypothalamic arcuate nucleus (ARC) of DiO rats (58%; P<0.05), as were 5-HT_2A receptor binding sites ([³H]ketanserin) in both the ARC (44%; P<0.05) and lateral hypothalamic area (LHA) (121%; P<0.05). However, binding to 5-HT_2C receptors ([³H]mesulgergine) in DiO rats was not significantly different from that in controls in any hypothalamic region. Binding to 5-HT transporters ([³H]paroxetine) was significantly increased (P<0.05) in both dorsal and median raphe, paraventricular nuclei (PVN), ventromedial nuclei (VMH), anterior hypothalamic area (AHA) and LHA of DiO rats, by 47%–165%. Tryptophan hydroxylase protein levels in the raphe nuclei were not significantly different between controls and DiO rats. In conclusion, we have demonstrated regionally specific changes in binding to certain 5-HT receptor subtypes in obesity induced by voluntary overeating of a palatable diet. Overall, these changes are consistent with reduced 5-HT release and decreased activity of the 5-HT neurons. Reduction in the hypophagic action of 5-HT, possibly acting at 5-HT_1A, 5-HT_1B and 5-HT_2A receptors, may contribute to increased appetite in rats presented with highly palatable diet.     

5-HT2A/C receptors mediate the antipsychotic-like effects of alstonine

The purpose of this study was to determine the effects of alstonine, an indole alkaloid with putative antipsychotic effects, on working memory by using the step-down inhibitory avoidance paradigm and MK801-induced working memory deficits in mice. Additionally, the role of serotonin 5-HT_2A/C receptors in the effects of alstonine on mouse models associated with positive (MK801-induced hyperlocomotion), negative (MK801-induced social interaction deficit), and cognitive (MK801-induced working memory deficit) schizophrenia symptoms was examined. Treatment with alstonine was able to prevent MK801-induced working memory deficit, indicating its potential benefit for cognitive deficits now seen as a core symptom in the disease. Corroborating previously reported data, alstonine was also effective in counteracting MK801-induced hyperlocomotion and social interaction deficit. Ritanserin, a 5-HT_2A/C receptor antagonist, prevented alstonine's effects on these three behavioral parameters. This study presents additional evidence that 5-HT_2A/C receptors are central to the antipsychotic-like effects of alstonine, consistently seen in mouse models relevant to the three dimensions of schizophrenia symptoms.     

Modification of 5-HT neuron properties by sustained administration of the 5-HT1A agonist gepirone: electrophysiological studies in the rat brain

The sustained administration of the 5-HT1A agonist gepirone (15 mg/kg/day, s.c.) in the rat produced an initial decrease of the firing activity of dorsal raphe 5-HT neurons which was followed by a progressive recovery to normal after 14 days of treatment. At this point in time, the effect of intravenous lysergic acid diethylamide (LSD) on the firing activity of 5-HT neurons was markedly reduced, whereas those of 8-hydroxy-2-N,N-propylamino-tetralin (8-OH-DPAT) and of gepirone were unchanged; however, the responsiveness of 5-HT neurons to direct microiontophoretic application of 5-HT, LSD, 8-OH-DPAT, and gepirone, but not of GABA, was reduced. The responsiveness of postsynaptic dorsal hippocampus pyramidal neurons to 5-HT, 8-OH-DPAT, and gepirone was not altered by the 14-day gepirone treatment. The effectiveness of the electrical stimulation of the ascending 5-HT pathway in reducing pyramidal neuron firing activity was not significantly modified in rats treated with gepirone for 14 days. Furthermore, this treatment did not alter the function of the terminal 5-HT autoreceptor. It is concluded that the progressive restoration of the firing activity of 5-HT neurons, due to a desensitization of the somatodendritic 5-HT autoreceptor, combined with the direct activation of normosensitive postsynaptic 5-HT1A receptor by gepirone, should result in an augmented tonic activation of postsynaptic 5-HT1A receptors. The progressive appearance of this phenomenon would be consistent with the time course of the clinical anxiolytic, and possibly antidepressant, effects of gepirone.     

Pre- and post-synaptic effects of the 5-HT3 agonist 2-Methyl-5-HT on the 5-HT system in the rat brain

Microiontophoretic applications of 5-HT and of the 5-HT₃ agonist 2-methyl-5-HT produced a current-dependent suppression of firing activity of both hippocampal (CA₁ and CA₃) and cortical neurons in anesthetized rats. Concomitant microiontophoretic applications of the 5-HT₃ antagonists BRL 46470A and S-zacopride, as well as their intravenous injection, did not antagonize the inhibitory effect of 5-HT and 2-methyl-5-HT. In contrast, the 5-HT_1A antagonist BMY 7378, applied by microiontophoresis or administered intravenously, significantly reduced the inhibitory action of 5-HT and 2-methyl-5-HT. The firing activity of dorsal raphe 5-HT neurons was also reduced by 5-HT, 2-methyl-5-HT and the 5-HT_1A agonist 8-OH-DPAT applied by microiontophoresis. While BRL 46470A (0.1 and 1 mg/kg, i.v.) did not antagonize the inhibitory effect of the three 5-HT agonists on 5-HT neuronal firing activity, only that of 8-OH-DPAT was attenuated by the 5-HT_1A antagonist (+) WAY 100135. R-zacopride significantly reduced the duration of suppression of firing activity of CA₃ pyramidal neurons induced by the electrical stimulation of the ascending 5-HT pathway, and this reducing effect was prevented by the three 5-HT₃/5-HT₄ antagonists renzapride, S-zacopride and tropisetron, but not by BRL 46470A. Finally, in in vitro superfusion experiments, both BRL 46470A and S-zacopride antagonized the enhancing action of 2-methyld-HT on the electrically-evoked release of [³H]-5-HT in both rat frontal cortex and hippocampus slices. These findings suggest that, in vivo, the suppressant effect of 2-methyl-5-HT on the firing activity of dorsal hippocampus pyramidal, somatosensory cortical, and dorsal raphe 5-HT neurons is not mediated by 5-HT₃ receptors, but rather by 5-HT_1A receptors. The attenuating effect of R-zacopride on the effectiveness of the stimulation of the ascending 5-HT pathway is not mediated by 5-HT₃ receptors. In contrast, in vitro, the enhancing action of 2-methyl-5-HT on the electrically-evoked release of [³H]5-HT in both frontal cortex and hippocampus slices is mediated by 5-HT₃ receptors. © 1995 Wiley-Liss, Inc.     

氯丙咪嗪治疗抑郁症的疗效与血浆5-HT含量的关系

目的　了解氯丙咪嗪治疗抑郁症的疗效与血浆 5 -羟色胺 (5 -HT)含量的关系。方法　符合CCMD - 2诊断标准的抑郁症病人 15例 (男 5例、女 10例 ) ,年龄 2 7～ 6 2岁 ,HAMD2 1～ 4 5分 ,纽卡斯尔量表 6～ 10分者进入本组。以不定剂量氯丙咪嗪口服 ,逐渐加量至 1周后各自剂量固定不变 ,疗程 8周。以HAMD减分率大于 5 0 %为有效指标。采用HPLC -ED测定治疗前、后血浆 5 -HT含量。结果　HAMD疗前为 (38 84± 6 5 3)分 ,疗后为(11 93± 5 93)分 (t=2 4 5 7,P <0 0 1) ;血 5 -HT疗前为 (186 6 2± 88 88)ng/ml,疗后为 (2 2 6 79± 5 8 72 )ng/ml(t=2 80 8,P <0 0 1) ;HAMD得分变化与血浆 5 -HT含量变化呈显著负相关 (r =- 0 85 6 ,P <0 0 1)。结论　氯丙咪嗪临床疗效与血浆 5 -HT上升呈正相关关系     

酒精戒断对清醒大鼠海马DG区部分兴奋性氨基酸的影响

目的探讨在清醒状态下大鼠长期饮酒停饮后出现戒断症状时海马DG(dentate gyrus)区部分兴奋性氨基酸含量变化。方法成年Wistar大鼠(300g~350g)40只随机分成对照组(n=10)和酒精组(n=30)。酒精组用50%酒精按10ml/kg/d灌胃1周(n=10)、2周(n=10)、4周(n=10),对照组给予同等剂量的生理盐水灌胃4周。用微透析法和高效液相色谱法分别测定末次饮酒6h、30h、48h、72h海马DG区谷氨酸及天冬氨酸含量,同时观察大鼠撤除酒精后不同时间戒断症状。结果2周酒精组及4周酒精组在末次饮酒30h、48h时,清醒大鼠海马DG区天冬氨酸及谷氨酸水平较末次饮酒6h显著上升(P<0.05),末次饮酒72h与末次饮酒6h无明显变化;兴奋性氨基酸含量升高时间与戒断症状明显出现时间基本一致;1周酒精组、对照组在上述各时段天冬氨酸及谷氨酸水平无显著变化。结论(1)酒精戒断症状与饮酒时间长短呈正相关;(2)酒精戒断综合征与海马DG区细胞外液兴奋性氨基酸神经递质含量增加有关。