Effect of agmatine on long-term potentiation in morphine-treated rats

Agmatine is an endogenous amine derived from l-arginine that potentiates morphine analgesia and inhibits naloxone precipitated abstinent symptoms in morphine dependent rats. In this study, the effects of agmatine on long-term potentiation (LTP) in the lateral perforant path (LPP)-granule cell synapse of the rat dentate gyrus (DG) on saline or morphine-treated rats were investigated. Population spikes (PS), evoked by stimulation of the LPP, was recorded from DG region. Acute agmatine (2.5-10 mg/kg, s.c.) treatment facilitated hippocampal LTP. Acute morphine (30 mg/kg, s.c.) treatment significantly attenuated hippocampal LTP and agmatine (10 mg/kg, s.c.) restored the amplitude of PS that was attenuated by morphine. Chronic morphine treatment resulted in the enhancement of hippocampal LTP, agmatine co-administered with morphine significantly attenuated the enhancement of morphine on hippocampal LTP. Imidazoline receptor antagonist idazoxan (5 mg/kg, i.p.) reversed the effect of agmatine. These results suggest that agmatine attenuated the effect of morphine on hippocampal LTP, possibly through activation of imidazoline receptor.     

吗啡依赖大鼠海马长时程增强改变及归元片的干预效应

目的:在体观察吗啡条件性位置偏爱(conditioned place preference,CPP)大鼠海马齿状回(dentate gyrus,DG)长时程增强(long-term potentiation,LTP)的变化,评价归元片自身有无依赖性以及对吗啡CPP和LTP的干预效应。方法:(1)连续给予吗啡(5mg·kg-1)7d,使大鼠产生明显的吗啡CPP,观察吗啡CPP的自然消退;(2)归元片(25mg·kg-1及50mg·kg-1)训练7d,d8测定大鼠对伴药箱的偏爱效应;(3)在归元片干预实验中,干预组在每次给予吗啡前15min分别给予不同剂量归元片(25、37.5mg·kg-1),观察归元片对吗啡CPP形成的影响。在以上模型的基础上,应用在体脑立体定位胞外记录技术测量海马齿状回LTP的变化。结果:(1)5mg·kg-1吗啡诱导大鼠对伴药侧产生显著性CPP;(2)归元片不能诱导大鼠形成CPP,同时也不影响DG-LTP;(3)吗啡CPP大鼠在高频刺激(high frequency stimulation,HFS)后,各时间点所记录的群体峰电位(population spikes,PS)相对幅值较对照组显著增高;(4)归元片25和37.5mg·kg-1均可拮抗吗啡CPP的获得,并能抑制吗啡对PS相对幅值的影响;(5)吗啡CPP在停用吗啡后12d消退,此时海马PS相对幅值与对照组比较无差异。结论:吗啡可诱导CPP,海马LTP在CPP形成时增强,在CPP消退后恢复正常,提示LTP参与药物成瘾过程。归元片自身不能诱导CPP,但可抑制吗啡CPP的获得与LTP的增强。     

Long-term potentiation in dentate gyrus of the rat is inhibited by the phosphoinositide 3-kinase inhibitor, wortmannin

The pivotal role of inositol phospholipids in cell signalling has been placed centre-stage again with the recognition that phosphoinositide (PI) 3-kinase is implicated in several cellular processes. Stimulation of PI-3 kinase requires activation of the 85 kD regulatory subunit which relies on tyrosine phosphorylation, one consequence of which is activation of the 110 kD catalytic subunit. In this study, we have investigated the role of PI 3-kinase in the expression of long-term potentiation (LTP) in perforant path-granule cell synapses of the rat. We report that intracerebroventricular injection of wortmannin inhibited expression of LTP, though it did not affect the early change in the synaptic response. Activation of PI 3-kinase was enhanced in tetanized tissue prepared from dentate gyrus, compared with untetanized tissue, but this effect was inhibited in tissue prepared from wortmannin-pretreated rats. LTP was associated with increased glutamate release, as previously described, but this effect was also inhibited in tissue prepared from wortmannin-pretreated rats. The results presented demonstrate that wortmannin also exerted an inhibitory effect on KCl-stimulated glutamate release and calcium influx in hippocampal synaptosomes in vitro. The evidence presented is consistent with the hypothesis that PI 3-kinase activation, possibly by NGF, plays a role in expression of LTP in dentate gyrus.     

Modulation of hippocampal long-term potentiation by the amygdala: a synaptic mechanism linking emotion and memory.

Why are emotionally arousing experiences well-remembered? Since the amygdala and hippocampus play pivotal roles in emotion and memory, respectively, the interaction between these brain regions may underlie the formation of enhanced memory for emotionally arousing events. Behavioral experiments using animals have demonstrated that lesions of the amygdaloid nuclei or infusions of drugs into the amygdaloid nuclei impair or enhance hippocampal-dependent learning. In addition, we have obtained direct evidence that neural inputs from the amygdala modulate synaptic plasticity in the hippocampus, through electrophysiological experiments using anesthetized rats. Electrical stimulation of the basolateral amygdala evoked synaptic potentials in the dentate gyrus of the hippocampus, indicating that there is a neural connection from the amygdala to the hippocampus. Lesion of the basolateral or basomedial, but not central, amygdala resulted in attenuation of long-term potentiation (LTP) at the perforant path-dentate gyrus granule cell synapses. High-frequency stimulation of the basolateral or basomedial amygdala alone did not induce LTP in the dentate gyrus, but facilitated the induction of LTP when applied at the same time as tetanic stimulation of the perforant path. The activity-dependent facilitation of hippocampal LTP by the basomedial and basolateral amygdala may be a synaptic mechanism underlying memory enhancement associated with emotions.     

Developmental lead (Pb) exposure reduces the ability of the NMDA antagonist MK-801 to suppress long-term potentiation (LTP) in the rat dentate gyrus, in vivo

Chronic developmental lead (Pb) exposure increases the threshold and enhances decay of long-term potentiation (LTP) in the dentate gyrus of the hippocampal formation. MK-801 and other antagonists of the N-methyl-D-aspartate (NMDA) glutamate receptor subtype impair induction of LTP. In addition, Pb exposure reduces presynaptic glutamate release and is associated with alterations in NMDA receptor expression. This study examined LTP in Pb-exposed animals challenged with a low dose of MK-801 to assess the sensitivity of this receptor to inhibition. Pregnant rats received 0.2% Pb acetate in the drinking water beginning on gestational day 16, and this regimen was continued through lactation. Adult male offspring maintained on this solution from weaning were prepared with indwelling electrodes in the perforant path and dentate gyrus. Several weeks later, input/output (I/O) functions were collected in awake animals before and after saline or MK-801 administration (0.05 mg/kg, s.c.). LTP was induced using suprathreshold train stimuli 60 min post-drug. Post-train I/O functions were reassessed 1 and 24 h after train delivery. Upon full decay of any induced LTP, drug conditions were reversed such that each animal was tested under saline and MK-801. I/O functions measured 1 and 24 h after train induction as well as immediate post-train responses revealed significant LTP of comparable magnitude that was induced in both control and Pb-exposed animals tested under saline conditions. In contrast, MK-801 reduced LTP in control but not in Pb-exposed animals. The broadening of the excitatory postsynaptic potential evident in responses evoked by train stimuli is NMDA-dependent. Pb exposure attenuated the MK-801-induced reduction in area of this NMDA component by approximately 50%. These findings are consistent with other neurochemical and behavioural observations and suggest that up-regulation of postsynaptic NMDA receptors produces subsensitivity to the inhibitory effects of MK-801 on hippocampal LTP following chronic developmental Pb exposure.     

An increased expression of the mGlu5 receptor protein following LTP induction at the perforant path-dentate gyrus synapse in freely moving rats

The involvement of metabotropic glutamate (mGlu) receptors in the induction of long-term potentiation (LTP) in vivo has been consistently documented. We have investigated whether LTP induction in the dentate gyrus of rats leads to changes in expression of mGlu2/3 or -5 receptor subtypes in the hippocampus. LTP was induced at the medial perforant path-dentate gyrus synapses, and mGlu receptor expression was examined by Western blot or in situ hybridization. An up-regulation of mGlu5 receptors was observed in the hippocampus both 24 and 48 h following LTP induction. This effect was restricted to the dentate gyrus and CA1 region, whereas no changes in mGlu5 receptor protein (but an increase in mRNA levels) were observed in the CA3 region. The increased expression of mGlu5 receptors was directly related to the induction of LTP, because it was not observed when tetanic stimulation was carried out in animals treated with the NMDA receptor antagonist, 2-amino-5-phosphonopentanoate (AP5). Western blot analysis also showed a reduced expression of mGlu2/3 receptors in the whole hippocampus 24 h after LTP induction, indicating that the increased expression of mGlu5 receptors was specific. These data suggest that an up-regulation of mGlu5 receptors is a component of the plastic changes that follow the induction of LTP at the perforant path-dentate gyrus synapse.     

(-),(+)黄皮酰胺对大鼠海马突触传递功能的不同影响

采用细胞外电生理记录法记录了低频刺激所诱发的麻醉大鼠海马齿状回颗粒细胞层群峰电位(PS)并比较了侧脑室注射(-),(+)黄皮酰胺对PS及强直刺激所诱导的长时程增强效应(LTP)作用。结果表明:低剂量(1nmol)时,(-)或(+)黄皮酰胺都对基础状态下的PS没有影响。对LTP(+)黄皮酰胺也无作用,(-)黄皮酰胺表现为增强作用;将剂量提高至4nmol时,(-)黄皮酰胺对基础PS和LTP都有增强作用且对LTP的作用表现出一定的剂量依赖性,(+)黄皮酰胺对PS仍无影响,对LTP有一定的抑制作用。提示黄皮酰胺对海马齿状回突触传递活动的作用具有光学选择性,这一结果有力地支持了(-)黄皮酰胺促智作用的行为学和神经生化学研究结果。     

Persistent (>24h) long-term depression in the dentate gyrus of freely moving rats is not dependent on activation of NMDA receptors, L-type voltage-gated calcium channels or protein synthesis

Hippocampal long-term depression (LTD) comprises a persistent reduction of synaptic strength that is typically induced by low frequency stimulation (LFS). Although LTD has been described for the dentate gyrus in vitro, this phenomenon in the dentate gyrus of the intact animal is less well understood. In the current study, we investigated the contribution of NMDA receptors, L-type voltage gated calcium channels and protein synthesis to LFS-induced LTD in the dentate gyrus of freely moving rats. Animals were implanted with electrodes to enable chronic measurement of evoked potentials from medial perforant path-dentate gyrus synapses. LTD persisted for at least 24h, and was unaffected by prior treatment with the NMDA receptor antagonists AP5 or ifenprodil, which, in contrast, prevented LTP. Neither the L-type voltage-gated calcium channel antagonist, methoxyverapamil, nor the protein translation inhibitors, anisomycin or emetine had an effect on the profile of LTD. Our results suggest that NMDA receptors and L-type voltage-gated calcium channels are not involved in the induction of LTD in the dentate gyrus in vivo. Intriguingly, persistent LTD can be established without the synthesis of new proteins, suggesting that in the dentate gyrus, alternative mechanisms exist for the sustainment of enduring LTD.     

Effects of glycine and structurally related amino acids on generation of long-term potentiation in rat hippocampal slices.

The effects of glycine and structurally related amino acids, serine, alanine and valine, on generation of long-term potentiation (LTP) of evoked potentials were investigated in the CA1, CA3 and dentate regions of rat hippocampal slices. In the Schaffer collateral-CA1 pyramidal cell synapses and in the perforant path-dentate granule cell synapses, glycine (5 x 10(-4) M) significantly enhanced the short-term potentiation (STP) induced by subthreshold tetanic stimulation, without affecting baseline responses. The effects of glycine resulted in generation of LTP in both synapses. On the other hand, glycine did not influence STP induced by subthreshold tetanus in the mossy fiber-CA3 pyramidal cell synapses. These results suggest that exogenous glycine can facilitate the generation of LTP in the CA1 region and in the dentate gyrus but not in the CA3 region. In the CA1 region and the dentate gyrus, D- and L-serine and D-alanine (10(-3) M) also showed the LTP-facilitating effects in a similar manner to glycine, but D- and L-valine had no effect on LTP generation. Furthermore, glycine and D-serine, but not L-valine, enhanced NMDA receptor-mediated synaptic responses in the absence of extracellular Mg2+. Together, these results make it probable that exogenously applied glycine and related amino acids facilitate the generation of LTP in the CA1 and dentate region by activating the glycine modulatory sites associated with NMDA receptors.     

一氧化氮供体对成年大鼠脑缺血后海马神经元再生的影响

目的　研究NO是否参与脑缺血后海马神经元再生。方法　血管内栓线法阻塞大脑中动脉 1.5h后再灌注 ,制备局灶脑缺血再灌性模型。脑缺血后 1h海马内输入 10 μLNO供体硝普钠 (0 .1mmol·L- 1)和维生素C(0 .4mmol·L- 1)。于脑缺血后 12 0h ,5 溴 2′ 脱氧尿嘧啶核苷 (BrdU)掺入法测定海马齿状回的细胞扩增。于再灌注后 2 4h测定海马诱导型一氧化氮合酶 (iNOS)活性及NO水平。结果在再灌注后d 8缺血侧海马齿状回的BrdU阳性细胞数比对照侧多大约 5倍 ,硝普钠和维生素C海马内输入显著增加脑缺血诱发的海马齿状回神经细胞扩增。结论　NO对脑缺血诱发海马齿状回神经元再生有重要作用     

The ethanol metabolite acetaldehyde inhibits the induction of long-term potentiation in the rat dentate gyrus in vivo.

1. Ethanol has been reported to inhibit the induction of long-term potentiation (LTP) in the hippocampus. However, the correlation between the effects of ethanol in vivo and in vitro remained unclear. In addition, previous works have little considered the possibility that the effect of ethanol is mediated by its metabolites. To solve these problems, we investigated the effects of ethanol and acetaldehyde, the first metabolite in the metabolism of ethanol, on the induction of LTP at medial perforant path-granule cell synapses in the dentate gyrus of anaesthetized rats in vivo. 2. Oral administration of 1 g kg-1 ethanol significantly inhibited the induction of LTP, confirming the effectiveness of ethanol in vivo. 3. A lower dose of ethanol (0.5 g kg-1) failed to inhibit the induction of LTP in intact rats, but significantly inhibited LTP in rats treated with disulfiram, an inhibitor of aldehyde dehydrogenase, demonstrating that LTP is inhibited by acetaldehyde accumulation following ethanol administration. 4. Intravenous injection of acetaldehyde (0.06 g kg-1) significantly inhibited the induction of LTP. 5. The inhibitory effect of acetaldehyde on LTP induction was also observed when it was injected into the cerebroventricules, suggesting that acetaldehyde has a direct effect on the brain. The intracerebroventricular dose of acetaldehyde effective in inhibiting LTP induction (0.1 - 0.15 mg brain-1) was approximately 10 fold lower than that of ethanol (1.0 - 1.5 mg brain-1). 6. It is possible that acetaldehyde is partly responsible for memory impairments induced by ethanol intoxication.     

The physical dependence liability of butorphanol: a comparative study with morphine.

In these studies, the physical dependence liability of butorphanol, a mixed 'agonist/antagonist' opioid analgesic, was compared to that of morphine. Male, Sprague-Dawley rats received i.c.v. infusions of saline (1 microliter/h), or an equimolar dose of butorphanol or morphine (52.3 nmol/h) for 3 days. The physical dependence liabilities of these two compounds were then compared by assessing both behavioral withdrawal signs and weight loss following naloxone-precipitated withdrawal. Body weight loss was also evaluated following abrupt (cessation of infusion) withdrawal from butorphanol or morphine. In animals receiving i.c.v. infusions of butorphanol or morphine, naloxone administration (5 mg/kg s.c.) induced an equivalent degree of body weight loss compared to saline-treated animals. In addition, the ED50 of naloxone to produce wet shakes, escape behavior, teeth chattering, urination and defecation was equivalent in rats receiving butorphanol or morphine. Infusions of butorphanol or morphine also produced an equivalent degree of weight loss in animals undergoing abrupt withdrawal. These results demonstrate then that a substantial degree of physical dependence had developed in rats which received a large dose of butorphanol.     

Tolerance and dependence following chronic intracerebroventricular infusions of Tyr-D-Arg2-Phe-Sar4 (TAPS)

The dermorphin-derived tetrapeptide Tyr-D-Arg(2)-Phe-Sar(4) (TAPS) was tested for its ability to induce tolerance, cross-tolerance, withdrawal and its substitution properties in rats subjected to chronic intracerebroventricular (i.c.v.) infusions of mu-opiate receptor agonists. Tolerance and cross-tolerance were assessed by quantification of the thermally induced tail-flick response. Chronic intracerebroventricular infusion of TAPS resulted in antinociception at almost 1000-fold lower doses compared to morphine sulphate and [D-Ala(2), MePhe(4)Gly(ol)(5)]enkephalin (DAMGO). Tolerance to the antinociceptive effect of TAPS developed similar to DAMGO and morphine sulphate. Cross-tolerance to intracerebroventricular bolus injections of DAMGO, but not of TAPS, was evident in rats rendered tolerant to morphine sulphate and TAPS. Naloxone-induced withdrawal was equally pronounced in animals treated with morphine sulphate, DAMGO or TAPS. TAPS substituted for morphine sulphate and vice versa regarding the withdrawal syndrome in a cross-over experimental design. In contrast to DAMGO, TAPS retains its antinociceptive effect following bolus administration in rats rendered tolerant to mu-opioid receptor agonists.     

脑脊液中D-Ser对齿状回颗粒细胞层突触传递和可塑性相关蛋白的作用研究

目的研究了脑脊液中D-丝氨酸(D-Ser)对齿状回颗粒细胞层突触传递和突触可塑性相关蛋白的作用。方法利用手术种植给药瘘管方法,在手术后第3天开始,隔天予以对照IgG和抗D-Ser IgG,给药3 d。之后采用胞外记录方法,刺激电极置于海马穿通纤维,记录齿状回颗粒细胞层LTP的诱导的变化,采用分子生物学方法检测皮层和海马突触可塑性相关蛋白表达的变化。结果抗D-Ser IgG连续中枢注射后,齿状回颗粒细胞层群峰电位的幅度明显下降,LTP的诱导受到明显阻断,同时海马和皮层部位突触可塑性相关蛋白的表达也发生了明显的变化。GAP-43在皮层和海马的表达分别升高约52%,58%。而MAP2的表达皮层降低约32%,海马降低约59%。皮层synapsinⅠ表达降低约45%,海马synapsinⅠ降低约57%。结论海马部位突触可塑性相关蛋白的表达对脑脊液中D-Ser浓度的变化表现出更高的敏感性,脑脊液中D-Ser具有重要的中枢调节作用,为神经精神相关疾病患者的临床治疗新药物和新方法的发现提供了理论支持。     

Loss of antinociceptive efficacy in rat pups infused with morphine from osmotic minipumps

We determined the susceptibility of two ages of rat pups to become tolerant to and dependent on morphine infusions from osmotic minipumps. Neonatal rats (postnatal day 6; P6) were infused for 72 h with morphine at 0.175 or 0.7 mg/kg/h. On P9, morphine's antinociceptive efficacy was reduced in both groups. P14 infant rats were also infused at 0.7 mg/kg/h. Unlike P9 neonates, morphine's potency was reduced in P17 infant rats, without a loss in efficacy. Yet raising the infusion rate to 1.1 mg/kg/h reduced morphine's efficacy. (3)H-DAMGO D-Ala2, N-MePhe4, Gly5-ol-enkephalin) binding revealed no change in the affinity or density of mu-opioid receptors at any age or in any treatment group. P9 and P17 pups were physically dependent on each infusion dose. Thus, chronic infusion of morphine affected both ages to such an extent that acutely administered morphine doses of even 1,000 mg/kg failed to restore antinociception. However, this effect cannot be attributed to changes in mu-opioid receptor number or affinity.     

腺苷A1受体和NMDA受体在海马齿状回突触传递活动中的关系

目的　探讨腺苷A1受体阻断剂对海马齿状回 (DG)突触传递活动的影响及其与NMDA受体的关系。方法采用在体记录麻醉大鼠LTP的电生理学方法 ,观察腺苷A1受体特异性阻断剂 8 环戊 1,3 二丙基黄嘌呤 (DPCPX)与NMDA受体激动剂、阻断剂在海马DG基础突触传递活动和高频刺激诱导的LTP中作用的相关性。结果　DPCPX(6mg·L- 1,5μL ,icv)或NMDA(0 2mg·L- 1,5μL ,icv)不影响大鼠海马DG突触传递活动 ,DPCPX对icvNMDA后高频刺激诱导已形成的LTP维持也无影响 ;预先给予DPCPX后则可显著增强NMDA的海马DG基础突触传递活动和LTP ;AP5(0 5mg·L- 1,5μL)阻断NMDA受体后对LTP的抑制作用不受DPCPX的影响 ,但预先给予DPCPX则可取消AP5 对LTP的抑制作用。结论　DPCPX不影响海马DG突触传递活动 ,但可影响NMDA受体的效应 ,增强NMDA受体在海马DG突触传递活动中的作用     

Increased expression, but not postsynaptic localisation, of ionotropic glutamate receptors during the late-phase of long-term potentiation in the dentate gyrus in vivo

Long-term potentiation (LTP) is extensively studied as a cellular mechanism of information storage in the brain. The induction and early expression mechanisms of LTP depend on activation and rapid modulation of ionotropic glutamate receptors. However, the mechanisms that underlie maintenance of LTP over the course of days or longer are poorly understood. Here, we have investigated the overall expression of AMPA- and NMDA-type glutamate receptors (AMPARs and NMDARs, respectively), as well as their levels at the synaptic surface membrane and in the postsynaptic density (PSD), in the dentate gyrus at 48 h following the induction of LTP at perforant path synapses in awake rats. We found a high-frequency stimulation-dependent increase in the overall levels of AMPAR subunits GluA1 and GluA2, but not GluA3 in the dentate gyrus. The increases in GluA1 and GluA2 levels were partially NMDAR-dependent, but were not found in biochemically isolated synaptic surface membrane or PSD fractions. In contrast, we found that the core NMDAR subunit, GluN1, increased in the synaptic surface-membrane fraction but it also was not targeted to the PSD. The GluA1 and GluA2 expression and the surface localisation of GluN1 returned to baseline levels by 2 weeks post-LTP induction. These data suggest that the late-phase LTP is not mediated by an overt increase in the AMPAR content of perforant path synapses. The increase in surface expression NMDARs may influence thresholds for future plasticity events.     

A role for inflammatory mediators in the IL-18 mediated attenuation of LTP in the rat dentate gyrus

Pro-inflammatory cytokines are known to be elevated in several pathological conditions that are associated with deficits in cognition. We have previously demonstrated that interleukin-18 (IL-18) inhibits long-term potentiation (LTP) in the dentate gyrus in vitro. In this study we have examined the involvement of the inflammatory mediators COX-2 and iNOS in IL-18-mediated inhibition of LTP. The effect of an anti-inflammatory PPARγ agonist was also investigated. We report that the impairment of LTP by IL-18 is significantly attenuated by prior application of the COX-2 inhibitor, SC-236 and the iNOS inhibitor 1400W. These agents had no effect on paired pulse depression in the dentate gyrus. Furthermore, application of the PPARγ agonist ciglitazone also attenuated IL-18-mediated inhibition of LTP. We discuss a role for p38 MAP kinase in these effects. This study provides novel evidence for the involvement of inflammatory mediators in IL-18-mediated inhibition of LTP in the rat dentate gyrus in vitro.     

Effects of carbachol on lead-induced impairment of the long-term potentiation/depotentiation in rat dentate gyrus in vivo.

The present study aims at evaluating the impairment of LTP and depotentiation (DP) of LTP induced by acute lead exposure, and the effects of peripheral carbachol (CCh) application on LTP/DP of acute and chronic lead-exposed rats in dentate gyrus in vivo. Rats (80-100 days) were acutely exposed to lead by intraperitoneal injection of 0.2% lead acetate (PbAc) solution (1.5mg/100g) and/or CCh (1 micro g/100g). Rats were chronically exposed to lead from parturition through adulthood (80-100 days) by the drinking of 0.2% PbAc solution and/or CCh (1 micro g/100g) chronic intraperitoneal injection one week. The input-output (I/O) function, paired-pulse reaction (PPR), excitatory postsynaptic potential (EPSP) and population spike (PS) amplitude were measured in response to stimulation applied to the lateral perforant path. Results showed that: first, acute lead exposure significantly depressed the amplitudes of LTP/DP of both EPSP slope and PS amplitude. Second, CCh significantly increased the amplitudes of both EPSP LTP/DP and PS LTP of acute Pb-exposed rats. After CCh treatment, the magnitudes of EPSP LTP/DP and PS LTP of acute Pb-exposed rats showed no significant difference with controls. Third, Chronic CCh application also reversed chronic Pb-induced impairment of PS LTP and EPSP DP of LTP. As CCh does not cross blood-brain barrier in healthy animals, the data suggest that CCh may traverse BBB in Pb-exposed animals and cure Pb-induced dysfunction of learning and memory.     

腺苷A1受体和NMDA受体在海马齿状回突触传递活动中的关系

目的探讨腺苷A₁受体阻断剂对海马齿状回(DG)突触传递活动的影响及其与NMDA受体的关系。方法 采用在体记录麻醉大鼠LTP的电生理学方法,观察腺苷A₁受体特异性阻断剂8-环戊-1,3-二丙基黄嘌呤(DPCPX)与NMDA受体激动剂、阻断剂在海马DG基础突触传递活动和高频刺激诱导的LTP中作用的相关性。结果DPCPX(6 mg·L^-1,5 μL,icv)或NMDA(0.2 mg·L^-1,5 μL,icv)不影响大鼠海马DG突触传递活动,DPCPX对icv NMDA后高频刺激诱导已形成的LTP维持也无影响;预先给予DPCPX后则可显著增强NMDA的海马DG基础突触传递活动和LTP;AP₅(0.5 mg·L^-1,5 μL)阻断NMDA受体后对LTP的抑制作用不受DPCPX的影响,但预先给予DPCPX则可取消AP₅对LTP的抑制作用。结论DPCPX不影响海马DG突触传递活动,但可影响NMDA受体的效应,增强NMDA受体在海马DG突触传递活动中的作用。