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1.
Yildiz Akar F Ulak G Tanyeri P Erden F Utkan T Gacar N 《Pharmacology, biochemistry, and behavior》2007,87(4):434-443
The role of nitric oxide (NO) on cognitive performance in a modified elevated plus-maze (mEPM) and passive-avoidance (PA) task was investigated by using the NO synthase (NOS) inhibitor 7-nitroindazole (7-NI) and an NO precursor l-arginine. The interaction between the activation of N-methyl-d-aspartate (NMDA) receptors and NO synthesis on memory retention was also studied. 7-NI, l-arginine or MK-801, a non-competitive NMDA receptor antagonist were injected intraperitoneally (i.p) to male Wistar rats 30 min before the first training session of the PA test or 30 min before on the first day testing (acquisition session) of mEPM task. Transfer latency, the time rat took to move from the open arm to the enclosed arm, was used as an index of learning and memory in a mEPM test. The retention session was performed 24 h after the acquisition one. In the PA task, the retention test was carried out 24 h after training and reduction of retention latency was used to evaluate the acquisition of learning and memory. Blood glucose level and locomotor activity of the rats was also evaluated. 7-NI (10, 20, 25, 50 mg/kg) and MK-801 (0.15 mg/kg) significantly prolonged the transfer latency on retention session in a mEPM test and shortened step-through latency in PA test. 7-NI-induced impairment in memory and learning was partly reversed by l-arginine (200 mg/kg), a competitive substrate for NOS. However subeffective doses of 7-NI (5 mg/kg) and MK-801 (0.075 mg/kg) given in combination significantly impaired plus-maze and PA performances in rats. Thus NMDA receptor mediated NO pathways may be implicated in the PA and mEPM behaviours in rats. Since 7-NI does not affect blood pressure and did not alter blood glucose level and locomotor activity in conscious rats, 7-NI-induced impairment of memory is not due to either hypertension, changes in blood glucose level or effects on locomotor activity. 相似文献
2.
Mark E. Bardgett Megan Points Jennifer Kleier Meredith Blankenship Molly S. Griffith 《Neuropharmacology》2010,59(6):492-502
Antagonists of H3-type histamine receptors exhibit cognitive-enhancing properties in various memory paradigms as well as evidence of antipsychotic activity in normal animals. The present study determined if a prototypical H3 antagonist, ciproxifan, could reverse the behavioral effects of MK-801, a drug used in animals to mimic the hypoglutamatergic state suspected to exist in schizophrenia. Four behaviors were chosen for study, locomotor activity, ataxia, prepulse inhibition (PPI), and delayed spatial alternation, since their modification by dizocilpine (MK-801) has been well characterized. Adult male Long-Evans rats were tested after receiving a subcutaneous injection of ciproxifan or vehicle followed 20 min later by a subcutaneous injection of MK-801 or vehicle. Three doses of MK-801 (0.05, 0.1, & 0.3 mg/kg) increased locomotor activity. Each dose of ciproxifan (1.0 & 3.0 mg/kg) enhanced the effect of the moderate dose of MK-801, but suppressed the effect of the high dose. Ciproxifan (3.0 mg/kg) enhanced the effects of MK-801 (0.1 & 0.3 mg/kg) on fine movements and ataxia. Deficits in PPI were observed after treatment with MK-801 (0.05 & 0.1 mg/kg), but ciproxifan did not alter these effects. Delayed spatial alternation was significantly impaired by MK-801 (0.1 mg/kg) at a longer delay, and ciproxifan (3.0 mg/kg) alleviated this impairment. These results indicate that some H3 antagonists can alleviate the impact of NMDA receptor hypofunction on some forms of memory, but may exacerbate its effect on other behaviors. 相似文献
3.
The effects of MK-801 upon motor activity and memory were assessed in a novel use of open-field behavior testing. In this
study, rats were treated with different doses of MK-801 (0.025, 0.05, 0.1 and 0.2 mg/kg) and given a brief 10-min exposure
to an open-field in which locomotor activity and within-session habituation were measured. Doses of MK-801 ≤0.1 mg/kg had
no effect upon locomotor activity or within-session habituation. MK-801 0.2 mg/kg produced a marked hyperlocomotion and completely
prevented within-session habituation. One day later, the animals were tested for their retention of habituation to evaluate
the effects of MK-801 on memory processes. In that animals treated with 0.2 mg/kg MK-801 failed to habituate to the novel
environment under the influence of 0.2 mg/kg MK-801, it was not surprising that these animals were impaired on the retention
test for the novel environment. Importantly, however, the 0.1 mg/kg MK-801 treatment, which did not affect locomotor activity
or within-session habitation to the novel environment, severely interfered with retention of the novel environment. Additional
experiments indicated that this result could not be accounted for by drug conditioning or drug state-dependent effects. Thus,
the results indicated that MK-801 can produce profound effects upon motor activity and memory and that these two effects can
be disassociated.
Received: 11 June 1997 / Final version: 5 January 1998 相似文献
4.
Mark E. Bardgett Megan Points John Roflow Meredith Blankenship Molly S. Griffith 《Psychopharmacology》2009,205(4):589-597
Rationale Recent studies have raised the possibility that antagonists of H3 histamine receptors possess cognitive-enhancing and antipsychotic properties. However, little work has assessed these compounds
in classic animal models of schizophrenia.
Objectives The purpose of this study was to determine if a prototypical H3 antagonist, thioperamide, could alter behavioral deficits caused by the N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801, in adult male rats. MK-801 was chosen to be studied since it produces a state
of NMDA receptor hypofunction in rats that may be analogous to the one hypothesized to occur in schizophrenia.
Methods The interaction between thioperamide and MK-801 was measured in three behavioral tests: locomotor activity, prepulse inhibition
(PPI), and delayed spatial alternation. In each test, rats received a subcutaneous injection of saline or thioperamide (3.0
and 10 mg/kg) followed 20 min later by a subcutaneous injection of saline or MK-801 (0.05, 0.10, and 0.30 mg/kg).
Results Locomotor activity was significantly elevated by MK-801 in a dose-dependent manner. Thioperamide pretreatment alone did not
alter locomotor activity; however, its impact on MK-801 was dose-dependent. Each thioperamide dose enhanced the effects of
two lower doses of MK-801 but reduced the effect of a higher MK-801 dose. Clear deficits in PPI and delayed spatial alternation
were produced by MK-801 treatment, but neither impairment was significantly modified by thioperamide pretreatment.
Conclusions H3 receptors modulate responses to NMDA antagonists in behaviorally specific and dose-dependent ways. 相似文献
5.
Zofia Rogóż 《Pharmacological reports : PR》2013,65(5):1401-1406
BackgroundSeveral clinical reports have suggested that the mirtazapine-induced augmentation of risperidone activity may effectively improve treatment of the negative and certain cognitive symptoms of schizophrenia.MethodsThe aim of the present study was to evaluate the effect of mirtazapine and risperidone, given separately or jointly, on the impact of MK-801(an NMDA receptor antagonist), given prior to the first introductory session, on the object recognition memory in mice. To this end, we used the object recognition test in which animals were tested for the ability to discriminate between an old, familiar and a novel object. Mirtazapine (2.5 or 5 mg/kg) and risperidone (0.01 mg/kg) were given 30 min before MK-801, and MK-801 (0.1 or 0.2 mg/kg) was administered 30 min before the first introductory session. Memory retention was evaluated 1.5 h after the introductory session.ResultsThe obtained results showed that MK-801 (0.2 mg/kg) decreased memory retention when given before the introductory session. Co-treatment with risperidone (0.01 mg/kg) and mirtazapine (2.5 or 5 mg/kg) abolished the effect of MK-801, whereas those drugs given separately did not change the action of MK-801.ConclusionsThe obtained results suggest that mirtazapine may enhance the antipsychotic-like effect of risperidone in the animal test modeling some cognitive symptoms of schizophrenia. Further studies are necessary to elucidate its mechanism of action. 相似文献
6.
Two experiments using a state-dependent retention (SDR) design determined whether MK-801 blocked the acquisition and retention of an avoidance response. In Experiments 1 and 2, rats were trained and tested 30 min after injections of either saline or MK-801 (0.05 and 0.10 mg/kg, respectively). Two minutes after training, subjects were immediately tested, and in both experiments, the avoidance response was acquired. The 24-h retention tests for Experiment 1 revealed that the data marginally supported a SDR interpretation. In Experiment 2, the dose of MK-801 was increased to 0.10 mg/kg, and the results showed that MK-801 rendered passive avoidance (PA) state-dependent. These experiments indicate that neither the 0.05 nor 0.10 mg/kg doses of MK-801 prevented acquisition of the avoidance response and that the latter dose rendered memory for PA training state-dependent. It is suggested that doses of MK-801 that did not impair PA learning can function as a cue state and influence expression of memory for PA. 相似文献
7.
de Oliveira RV Dall'Igna OP Tort AB Schuh JF Neto PF Santos Gomes MW Souza DO Lara DR 《Behavioural pharmacology》2005,16(2):79-84
N-Methyl-D-aspartate (NMDA) receptor antagonists cause hyperlocomotion and cognitive deficits in rodents, and caffeine-tolerant mice show diminished locomotor response to NMDA receptor antagonists. The aim of this study was to evaluate the effect of subchronic caffeine treatment on MK-801-induced hyperlocomotion, ataxia and cognitive deficits, as well as amphetamine-induced hyperlocomotion in mice. Mice were treated subchronically with caffeine (0, 0.1, 0.3 and 1 mg/ml and 1, 3 and 7 days) and evaluated for locomotor activity, working memory (delayed alternation test), long-term memory (inhibitory avoidance task) and ataxia. Hyperlocomotion induced by MK-801 (0.25 mg/kg i.p.) was diminished after 3 days and almost abolished after 7 days of caffeine treatment at the 1 mg/ml dose, and this effect was also dose-dependent. Ataxia induced by 0.5 mg/kg MK-801 was not affected by caffeine treatment, but a short-lived hyperlocomotor effect was observed. Performance deficit in the inhibitory avoidance task induced by MK-801 (0.01 mg/kg) was prevented in mice treated with caffeine for 7 days at 1 mg/ml, and perseverative errors in the T-maze by MK-801 (0.4 mg/kg) were attenuated. The locomotor effect of amphetamine (5 mg/kg) was unaffected by subchronic caffeine treatment. The findings that hyperlocomotion and cognitive effects induced by MK-801 can be specifically influenced by reduced adenosinergic activity agree with a model of adenosine hypofunction in schizophrenia, since NMDA receptor antagonists are pharmacological models for this disorder. 相似文献
8.
K Wedzony M Ma?kowiak W Zajaczkowski K Fija? A Chocyk A Czyrak 《Neuropsychopharmacology》2000,23(5):547-559
In the present study, we investigated whether the antagonist of 5-HT1A receptors, WAY 100135, was capable of modifying the psychostimulant and psychotomimetic effects of MK-801, a non-competitive antagonist of NMDA receptors. It was found that: 1) WAY 100135 (10 and 20 mg/kg, but not 1.25, 2.5, and 5 mg/kg) transiently, in a dose dependent manner, attenuated the locomotor stimulant effects of MK-801 (0.4 mg/kg). Given alone, WAY 100135 had no effect on the locomotor activity of rats; 2) WAY 100135 (1.25 and 2.5 mg/kg, but not 10 or 20 mg/kg), attenuated or abolished the disruptive effects of MK-801 on the sensorimotor gating measured in a prepulse-induced inhibition of the acoustic startle response paradigm. WAY 100135 in all tested doses had no effect on the sensorimotor gating or amplitude of the acoustic startle response; 3) WAY 100135 (1.25, 2.5 mg/kg, but not 5 mg/kg) attenuated the detrimental effects of MK-801 on working memory and selective attention, measured in a delayed alternation task. Again, given alone, WAY 100135 did not influence the behavior of rats in that experimental paradigm; and 4) MK-801 (0.4 mg/kg) had no effect on the 5-HT1A receptor mRNA level in rat hippocampus, measured 2 and 24 hours after MK-801 administration. These data indicate that 5-HT1A receptors might be involved in the psychotomimetic effects of non-competitive NMDA receptor antagonists. In addition, 5-HT1A serotonin receptor antagonists and partial agonists may have potential antipsychotic properties. 相似文献
9.
There is consistent experimental evidence that noncompetitive antagonists of the N-methyl--aspartate (NMDA) receptor, such as ketamine, MK-801, and phencyclidine (PCP), impair cognition and produce psychotomimetic effects in rodents. Nitric oxide (NO) is considered as an intracellular messenger in the brain. The implication of NO in learning and memory is well documented. This study was designed to investigate the ability of the NO synthase inhibitor -NAME to antagonize recognition and spatial memory deficits produced by the NMDA receptor antagonists, MK-801 and ketamine, in the rat. -NAME (1–3 mg/kg) counteracted MK-801- (0.1 mg/kg) and ketamine (3 mg/kg)-induced performance impairments in the novel object recognition task. -NAME (10 mg/kg) attenuated ketamine (15 mg/kg)-induced spatial working memory and retention deficits in the radial water maze paradigm. -NAME, applied at 3 mg/kg, however, disrupted rodents'' performance in this spatial memory task. The present findings indicate (1) that -NAME is sensitive to glutamate hypofunction produced by other than PCP NMDA antagonists such as MK-801 and ketamine and (2) that -NAME alone differentially affects rodents'' spatial memory. 相似文献
10.
Blocking glutamatergic transmission at the N-methyl-d-aspartate (NMDA) receptor complex with MK-801 (0.15–0.5 mg/kg, IP) was found to induce a robust, dose-dependent increase in locomotor activity. This behavioural activation was similar in intensity to that observed afterd-amphetamine (1 mg/kg, SC). The locomotor stimulation induced by MK-801 at 0.3 mg/kg was significantly inhibited by the D2 dopamine receptor antagonist raclopride (0.1–0.3 mg/kg, SC) and by the D1 receptor antagonist SCH 23390 (0.04 mg/kg, SC). The locomotor activity induced by a higher dose of MK-801 (0.5 mg/kg) was reduced by higher doses of raclopride or SCH 23390 administered alone (0.3 and 0.08 mg/kg, respectively), and was inhibited by simultaneous administration of ineffective doses. Raclopride significantly reducedd-amphetamine-induced locomotor activity at a dose (0.2 mg/kg) that also blocked the effects of a low dose of MK-801. In contrast, SCH 23390 blocked the effects ofd-amphetamine at a dose (i.e. 0.01 mg/kg) lower than that needed to block MK-801. These results suggest that the dopaminergic system may in part mediate the locomotor effects induced by the NMDA antagonist, MK-801, in rats. However, the locomotor activity induced by MK-801 appears to be less sensitive to dopaminergic receptor blockade than that induced byd-amphetamine, suggesting that the underlying mechanisms, although similar, are not identical. 相似文献
11.
Mervi Pitknen Jouni Sirvi Ewen MacDonald Suvi Niemi Tommi Ekonsalo Paavo Riekkinen Sr. 《European neuropsychopharmacology》1995,5(4)
The present study was undertaken to investigate the effects of modulation of the
(NMDA) receptor on learning and memory. Thus, the performance of rats treated with
-cycloserine, a partial agonist at the glycine recognition site of the NMDA receptor complex, and MK-801, a noncompetitive NMDA receptor antagonist, either alone or concurrently were assessed in radial arm maze and water maze tasks. Administration of MK-801 (0.1 mg/kg, i.p.) impaired acquisition in the water maze (increased escape latency and distance) and working memory in the radial arm maze (increased re-entries) in rats. Moreover, in the radial arm maze, MK-801 disrupted locomotion (increased latencies and decreased arm entries per minute) and impaired the acquisition of reference memory (increased number of errors) performance of rats.
-Cycloserine (0.03, 0.3, 1.0, 3.0, 10 mg/kg, i.p.) had no effects on acquisition or memory performance of control or MK-801-treated rats in either of these tasks. However,
-cycloserine (0.03, 0.3, 3.0 mg/kg) reversed the MK-801-induced disruption in locomotion. Furthermore, 3.0 mg/kg
-cycloserine increased behavioral activity and also decreased the time needed to complete the task in control animals. To conclude, our results suggest that the consequences of NMDA receptor modulation on learning and memory processes and sensorimotor functions may be functionally different or have distinct anatomical locations. 相似文献
12.
Rationale: There is some strong evidence about the role of nitric oxide (NO) as an intercellular messenger in central physiological
mechanisms. NO is synthesized from l-arginine by nitric oxide synthase (NOS), as a response to activation of N-methyl-d-aspartate (NMDA) receptors by excitatory amino acids. NMDA receptor antagonists also produce antidepressant-like actions
in preclinical models. Objective: In the present study, the involvement of NO in the mechanism of depression was investigated. 7-Nitroindazole (7-NI) (15,
30, 60, 90 mg/kg IP), a selective inhibitor of neuronal NOS was examined. Methods: The Porsolt forced swimming test (FST) has been used as a test for screening new antidepressant agents. Results: 7-NI dose-dependently decreased the immobility time in FST, but produced no significant change in locomotor activity in naive
rats. Neither l-arginine, nor d-arginine (100 mg/kg) affected the immobility time in the FST or revealed any effect on locomotion. l-Arginine but not d-arginine, given 10 min before 7-NI, reversed the 7-NI-induced effect on immobility time. Conclusion: Our findings suggest that NO might be an important modulator of depression in rats.
Received: 3 June 1999 / Final version: 30 September 1999 相似文献
13.
Effects of selective inhibition of N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) on mice in learning and memory tasks 总被引:1,自引:0,他引:1
The purpose of the present study was to examine the effects of 2-(phosphonomethyl)-pentanedioic acid (2-PMPA), a selective inhibitor of N-acetylated-alpha-linked-acidic dipeptidase (NAALADase, glutamate carboxypeptidase II), an enzyme catalyzing the cleavage of glutamate from the neuropeptide N-acetyl-aspartyl-glutamate (NAAG), on memory processes in mice. Long-term memory was evaluated in step-through passive avoidance task while alternation behavior, as a measure involving spatial working memory, was assessed in Y-maze task. Additionally, horizontal activity was evaluated by means of electronically monitored locomotor activity system. The mice were treated with either 2-PMPA (50, 100 and 150 mg/kg i.p.) or N-methyl-d-aspartate (NMDA) receptor antagonist, (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate (MK-801) at doses of: 0.05, 0.1, 0.15 and 0.2 mg/kg i.p., as a comparator. In the passive avoidance task, the drugs were administered once before or immediately after training, and before retention test. 2-PMPA at the doses used did not affect retention of passive avoidance; however, it increased the latency to enter the dark box during the training day. In the Y-maze task, 2-PMPA (150 mg/kg i.p.) impaired spontaneous alternation and reduced locomotion while the lower dose of 100 mg/kg was ineffective. In the locomotor activity test, 2-PMPA (100 and 150 mg/kg i.p.) did not significantly affect horizontal activity. MK-801 (0.2 mg/kg i.p.) injected before training reduced retention in the passive avoidance task. In the Y-maze task, MK-801 (0.1 mg/kg i.p.) impaired alternation behavior and considerably increased locomotion in the Y-maze and locomotor activity test. These results indicate that NAALADase inhibition may impair alternation behavior. 相似文献
14.
Mervi Pitkänen Jouni Sirviö Ewen MacDonald Suvi Niemi Tommi Ekonsalo Paavo Riekkinen Sr. 《European neuropsychopharmacology》1995,5(4):457-463
The present study was undertaken to investigate the effects of modulation of the (NMDA) receptor on learning and memory. Thus, the performance of rats treated with d-cycloserine, a partial agonist at the glycine recognition site of the NMDA receptor complex, and MK-801, a noncompetitive NMDA receptor antagonist, either alone or concurrently were assessed in radial arm maze and water maze tasks. Administration of MK-801 (0.1 mg/kg, i.p.) impaired acquisition in the water maze (increased escape latency and distance) and working memory in the radial arm maze (increased re-entries) in rats. Moreover, in the radial arm maze, MK-801 disrupted locomotion (increased latencies and decreased arm entries per minute) and impaired the acquisition of reference memory (increased number of errors) performance of rats. d-Cycloserine (0.03, 0.3, 1.0, 3.0, 10 mg/kg, i.p.) had no effects on acquisition or memory performance of control or MK-801-treated rats in either of these tasks. However, d-cycloserine (0.03, 0.3, 3.0 mg/kg) reversed the MK-801-induced disruption in locomotion. Furthermore, 3.0 mg/kg d-cycloserine increased behavioral activity and also decreased the time needed to complete the task in control animals. To conclude, our results suggest that the consequences of NMDA receptor modulation on learning and memory processes and sensorimotor functions may be functionally different or have distinct anatomical locations. 相似文献
15.
Effects of NMDA receptor antagonists on passive avoidance learning and retrieval in rats and mice 总被引:4,自引:0,他引:4
The effects of NMDA antagonists on passive avoidance learning, shock sensitivity and locomotor activity were examined. Pre-training administration of the antagonists 3-((±)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) in mice and rats resulted in impaired performance in a retention test 24 h later. No such impairment resulted from immediate post-training administration of either compound in either species. In addition neither compound, given only before the retention test, reduced the retention latencies of mice. In rats CPP was similarly ineffective whereas MK-801 reduced retention latencies, but only at a dose which significantly elevated locomotor activity at the time of the retention test. As assessed by vocalization threshold in mice and by the proportion of animals vocalizing in response to the passive avoidance training shock, neither compound produced analgesia. The vocalization threshold was, in fact, slightly reduced by both compounds. MK-801, but not CPP, stimulated locomotor activity in mice. These results indicate that in the passive avoidance task activation of NMDA receptors is involved in memory formation, but is not critical for the maintenance of memory or its retrieval. 相似文献
16.
The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) (0.08 and 0.12 mg/kg, i.p.) was used to examine whether spatial memory is learned state-dependently. Rats pre-treated with drug or saline were trained for 9 days in an eight-arm radial maze, in which four arms were baited. On the tenth day MK-801-treated rats were injected with saline and one group of saline-treated rats were injected with MK-801 (0.12 mg/kg) while another received saline. Performance of spatial memory was analysed for state-dependency. Neither rats treated with 0.08 mg/kg nor 0.12 mg/kg of MK-801 for 9 days were impaired in recall of spatial memory under saline. However, MK-801 impaired acquisition of spatial memory, with deficits in working memory and less marked deficits in reference memory. Motor activity (speed) was enhanced at both doses. Thus, learning under NMDA receptor blockade does not necessarily produce a condition that impedes the expression of the learning task under a different condition. 相似文献
17.
Fabiana K. Ludka Andréa D.E. Zomkowski Mauricio P. Cunha Tharine Dal-Cim Ana Lúcia B. Zeni Ana Lúcia S. Rodrigues Carla I. Tasca 《European neuropsychopharmacology》2013,23(5):400-412
Atorvastatin is a synthetic and lipophilic statin that presents a good effect in decreasing cholesterol levels and is safe and well tolerated. Population-based studies have suggested a positive role of statins in reducing depression risk. This study aimed at investigating the atorvastatin effect in the tail suspension test (TST) and in the forced swimming test (FST). The participation of NMDA receptors and l–arginine–NO–cGMP in an atorvastatin antidepressant-like effect in the TST was evaluated. Acute atorvastatin administration (0.1–30 mg/kg) reduced the immobility time both in TST and FST. A similar effect was observed by using imipramine as a positive control in the TST and FST (1 and 0.1–1 mg/kg, p.o., respectively). An atorvastatin (0.1 mg/kg) antidepressant-like effect was prevented by the pretreatment of mice with NMDA (0.1 pmol/site, i.c.v.), l-arginine (750 mg/kg, i.p.) or sildenafil (5 mg/kg, i.p.). The administration of MK-801 (0.001 mg/kg, i.p.), ketamine (0.1 mg/kg, i.p.), 7-nitroindazole (50 mg/kg, i.p.), methylene blue (20 mg/kg, i.p.), or ODQ (30 pmol/site i.c.v.) in combination with a subeffective dose of atorvastatin (0.01 mg/kg, p.o.) reduced the immobility time in the TST compared to drugs alone, showing the participation of the pathway l-arginine–NO–cGMP. The administration of drugs did not produce any significant alteration in locomotor activity in the open-field test. Acute atorvastatin treatment (0.1–10.0 mg/kg, v.o.) increased the hippocampal BDNF levels, which is an effect that has not been observed in imipramine-treated mice. These results demonstrate that atorvastatin exerts an antidepressant-like effect and point to dependence on the inhibition of NMDA receptors and NO–cGMP synthesis, and on the increase of hippocampal BDNF levels. 相似文献
18.
Repeated administration of electroconvulsive stimuli (ECS) to mice once daily for a period of 7 days results in an enhanced locomotor response induced by apomorphine (1.0 mg/kg, IP). Pretreatment (30 min) with the N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801 (0.01–1.0 mg/kg IP), suppressed ECS-induced seizure activity in a dose-dependent manner. MK-801 (0.01 and 0.033 mg/kg, IP) given 30 min before each ECS dose-dependently decreased apomorphine-mediated responses. Administration of MK-801 (0.033 mg/kg IP) 30 min after each convulsion had the same effect. These results indicate that MK-801 can abolish the ECS-induced enhancement of dopamine-mediated behaviour possibly by interfering with postictal processes. Thus, NMDA receptors seem to be involved in the behavioural changes and presumably also in the neural adaptations produced by repeated ECS. 相似文献
19.
Role of nitric oxide synthase inhibitors and NMDA receptor antagonist in nicotine-induced behavioral sensitization in the rat 总被引:4,自引:0,他引:4
Shim I Kim HT Kim YH Chun BG Hahm DH Lee EH Kim SE Lee HJ 《European journal of pharmacology》2002,443(1-3):119-124
Repeated injections of nicotine are well known to produce progressively larger increases in locomotor activity, an effect defined as behavioral sensitization. This study was carried out to investigate the role of nitric oxide (NO) and N-methyl-D-aspartate (NMDA) receptors in nicotine-induced behavioral sensitization. Rats were given repeated injections of nicotine (0.4 mg/kg, s.c., twice daily for 7 days) followed by one challenge injection on the fourth day after the last daily injection. Systemic challenge with nicotine produced a much larger increase in locomotor activity in nicotine-pretreated rats. Rats were pretreated with the nonselective nitric oxide synthase (NOS) inhibitor, N(G)-nitro-arginine-methyl-ester (L-NAME; 75 mg/kg, i.p.), the selective constitutive NOS inhibitor, N-nitro-L-arginine (L-NNA; 15 mg/kg, i.p.), the prototypical selective inducible NOS inhibitor, aminoguanidine (100 mg/kg, i.p.) or NMDA receptor antagonist, MK-801 ((5R,10S)-(+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine; 0.3 mg/kg, i.p.), 30 min before injections of nicotine during a 7-day development or a 3-day withdrawal phase after which challenged with nicotine on day 11. Pretreatment with L-NAME, L-NNA and MK-801, but not aminoguanidine, blocked the development of nicotine-induced sensitization to subsequent nicotine challenge. Injections of MK-801 twice daily during 3-day withdrawal periods after a 7-day induction period of nicotine attenuated nicotine-induced behavioral sensitization, whereas injections of L-NAME, L-NNA or aminoguanidine had no effects on the expression of sensitization produced by repeated nicotine. This study demonstrates that NMDA receptors can play a major role in the expression as well as development of nicotine-induced behavioral sensitization, and that NO is also involved in the development, but not critically involved in the expression of behavioral sensitization to nicotine. 相似文献
20.
MK-801 inhibits l-DOPA-induced abnormal involuntary movements only at doses that worsen parkinsonism
Melanie A. Paquette Akari M. Anderson Charles K. Meshul Steven W. Johnson S. Paul Berger 《Neuropharmacology》2010,58(7):1002-1008
Amantadine and dextromethorphan suppress levodopa (l-DOPA)-induced dyskinesia in Parkinson's disease patients and abnormal involuntary movements (AIMs) in the 6-hydroxydopamine (6-OHDA) rat model. These medications have been hypothesized to exert their therapeutic effects by a noncompetitive N-methyl-d-aspartate (NMDA) antagonist mechanism, but they also have known serotonin (5-HT) indirect agonist effects that could suppress AIMs. This raised the possibility that NMDA antagonists lacking 5-HTergic effects would not have the anti-dyskinetic action predicted by previous investigators. To test this hypothesis, we investigated MK-801, the most widely-studied NMDA antagonist. We found that chronic low-dose MK-801 (0.1 mg/kg) had no effect on development of AIMs or contraversive rotation. In addition, in l-DOPA-primed rats, low-dose MK-801 (0.1 mg/kg) had no effect on expression of AIMs, contraversive rotation, or sensorimotor function. Conversely, higher doses of MK-801 (0.2-0.3 mg/kg) suppressed expression of AIMs. However, as we show for the first time, anti-dyskinetic doses of MK-801 also suppressed l-DOPA-induced contralateral rotation and impaired sensorimotor function, likely due to non-specific interference of MK-801 with l-DOPA-induced behavior. We conclude that noncompetitive NMDA antagonists are unlikely to suppress dyskinesia clinically without worsening parkinsonism. 相似文献