Impairment Of Passive Avoidance Performance Research Articles

Minocycline alleviated scopolamine-induced amnesia by regulating antioxidant and cholinergic function

Background and aimMinocycline, a tetracycline derivative, has been found to exert neuroprotective properties. The current project aimed to assess the antioxidant status and cholinergic function in the amnesia induced by scopolamine. MethodsWe evaluated the passive avoidance performance, acetylcholine esterase (AChE) enzyme activity, and the oxidative stress indicators in the following groups: Normal control, scopolamine, and the treatment groups (the animals were given minocycline (10–30 mg/kg)). ResultsScopolamine (intraperitoneal) injection was associated with impairment of passive avoidance performance and neurotoxicity. Minocycline pronouncedly ameliorated scopolamine injury as presented by the increased latency time to darkness and stay time in lightness along with the decreased darkness entry. Moreover, minocycline decreased lipid peroxidation, while it elevated the levels of superoxide dismutase, AChE enzymes, and thiol groups in both the cortex and hippocampus. ConclusionOur data suggested that minocycline modulated the antioxidant status and AChE in the brains, which may contribute to its protective effects against scopolamine-induced amnesia.

AMPA receptors mediate passive avoidance deficits induced by sleep deprivation

The present study addressed the effects of sleep deprivation (SD) on AMPA receptor (AMPAR) binding in brain regions associated with learning and memory, and investigated whether treatment with drugs acting on AMPAR could prevent passive avoidance deficits in sleep deprived animals. [3H]AMPA binding and GluR1 in situ hybridization signals were quantified in different brain regions of male Wistar rats either immediately after 96h of sleep deprivation or after 24h of sleep recovery following 96h of sleep deprivation. Another group of animals were sleep deprived and then treated with either the AMPAR potentiator, aniracetam (25, 50 and 100mg/kg, acute administration) or the AMPAR antagonist GYKI-52466 (5 and 10mg/kg, acute and chronic administration) before passive avoidance training. Task performance was evaluated 2h and 24h after training. A significant reduction in [3H]AMPA binding was found in the hippocampal formation of SD animals, while no alterations were observed in GluR1 mRNA levels. The highest dose of aniracetam (100mg/kg) reverted SD-induced impairment of passive avoidance performance in both retention tests, whereas GYKI-52466 treatment had no effect. Pharmacological enhancement of AMPAR function may revert hippocampal-dependent learning impairments produced after SD. We argue that such effects might be associated with reduced AMPAR binding in the hippocampus of sleep deprived animals.

The ameliorating effects of LiuWei Dihuang Wang on cycloheximide-induced impairment of passive avoidance performance in rats

The ameliorating effects of aqueous and ethanolic extracts of LiuWei Dihuang Wang (LDW W and LDW E) after single, 1-week or 2-week consecutive treatment on the cycloheximide-induced amnesia by using the passive avoidance task in rats were studied. After single treatment, LDW W and LDW E (1 and 2 g/kg) significantly prolonged the shortened step-through latency induced by CXM and their potency was equal. LDW W at 1 g/kg after 1-week consecutive treatment or at 0.1 g/kg after 2-week consecutive treatment almost completely reversed CXM-induced amnesia. LDW W at any dose alone after single, 1-week or 2-week consecutive treatment did not influence the step-through latency in the training trial in rats. Furthermore, muscarinic antagonist scopolamine, peripheral cholinergic antagonist scopolamine methylbromide, serotonin precursor 5-hydroxytryptamine and serotonin releaser p-chloroamphetamine could block the ameliorating effects of LDW W. GABA A receptor antagonist bicuculline and GABA B receptor agonist baclofen also blocked the ameliorating effects of LDW W. These results suggest that the ameliorating effects of LDW whose potency were parallel to treatment duration might be related to activating peripheral cholinergic neuronal system and modulating the central nervous system.

Effect of Choto-san, a Kampo medicine, on impairment of passive avoidance performance in senescence accelerated mouse (SAM).

Effect of Choto-san (TJ-47), a Kampo medicine, on impairment of learning performance was evaluated by means of a step-through passive avoidance task in SAMP8 mice, a senescence-prone substrain. Tokishakuyaku-san (TJ-23), another Kampo medicine, was also employed for comparison. SAMP8 mice at the age of 10-12 months showed a poorer passive avoidance response than SAMR1 mice, a senescence-resistant substrain, in the memory-retention test, but not in the memory-acquisition test. Improved response in the memory-retention test was observed in SAMP8 mice treated with TJ-47, and almost equal degree of improvement was also observed after treatment with TJ-23. These results suggest that a long-term administration of Choto-san could improve to some extent the impairment of memory caused by aging.

Ameliorative effects of paeoniflorin, a major constituent of peony root, on adenosine A1 receptor-mediated impairment of passive avoidance performance and long-term potentiation in the hippocampus.

We examined the effects of paeoniflorin on adenosine A1 receptor-mediated memory disturbance in the mouse passive avoidance test and inhibition of long-term potentiation (LTP) in the rat hippocampal CA1 region. The pretraining administration of the selective adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) significantly impaired the retention performance determined 24 h after the training test. The intraperitoneal injections of paeoniflorin and the adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) significantly attenuated the deficit in retention performance caused by CPA. The in vitro studies revealed that adenosine (1 and 10 microM) dose dependently reduced both the population spike (PS) amplitudes and the tetanic stimulation-induced LTP in the hippocampus. DPCPX, at the concentration (0.1 microM) that had no effect on PS amplitudes or LTP induction, significantly reversed the suppressive effects of adenosine on both indices. Paeoniflorin also dose dependently reversed 10 microM adenosine-induced suppression of LTP but had no effect on PS reduced by adenosine. These results suggest that paeoniflorin ameliorates memory disruption mediated by adenosine A1 receptor and that modulation of adenosine-mediated inhibition of LTP in the hippocampus is implicated in its beneficial effect on learning and memory impairment in rodents.

Effects of Uncaria tomentosa total alkaloid and its components on experimental amnesia in mice: elucidation using the passive avoidance test.

The effects of Uncaria tomentosa total alkaloid and its oxindole alkaloid components, uncarine E, uncarine C, mitraphylline, rhynchophylline and isorhynchophylline, on the impairment of retention performance caused by amnesic drugs were investigated using a step-down-type passive avoidance test in mice. In this test, the retention performance of animals treated with the amnesic and test drugs before training was assessed 24 h after training. Uncaria tomentosa total alkaloid (10-20 mg kg(-1), i.p.) and the alkaloid components (10-40 mg kg(-1), i.p.), as well as the muscarinic receptor agonist oxotremorine (0.01 mg kg(-1), i.p.), significantly attenuated the deficit in retention performance induced by the muscarinic receptor antagonist scopolamine (3 mg kg(-1), i.p.). The effective doses of uncarine C and mitraphylline were larger than those of other alkaloid components. Uncarine E (20 mg kg(-1), i.p.) also blocked the impairment of passive avoidance performance caused by the nicotinic receptor antagonist mecamylamine (15 mg kg(-1), i.p.) and the N-methyl-D-aspartate (NMDA) receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 7.5 mg kg(-1), i.p.), but it failed to affect the deficit caused by the benzodiazepine receptor agonist diazepam (2 mg kg(-1), i.p.). Rhynchophylline significantly reduced the mecamylamine-induced deficit in passive avoidance behaviour, but it failed to attenuate the effects of CPP and diazepam. These results suggest that Uncaria tomentosa total alkaloids exert a beneficial effect on memory impairment induced by the dysfunction of cholinergic systems in the brain and that the effect of the total alkaloids is partly attributed to the oxindole alkaloids tested. Moreover, these findings raised the possibility that the glutamatergic systems are implicated in the anti-amnesic effect of uncarine E.

Effect of Choto-san, a kampo medicine, on impairment of passive avoidance performance in mice.

In mice with procephalic ischaemia loading, disrupted passive avoidance retention performance was dose-dependently improved by Choto-san, but this effect was antagonized by NAN-190, a serotonin1A receptor antagonist. In mice with decreased intracerebral serotonin concentration, Choto-san prevented disturbance in acquiring a passive avoidance response after scopolamine administration, but did not influence the decreased serotonin concentration. These results suggested that Choto-san showed the anti-amnestic effect based on the stimulation of serotonin1A receptors.

Reduction of 4-cyclohexyl-1-[(1R)-1,2-diphenylethyl]-piperazine-induced memory impairment of passive avoidance performance by sigma 1 receptor agonists in mice.

Intraperitoneal administration of 4-cyclohexyl-1-[(1R)-1,2-diphenylethyl]-piperazine (CDEP) immediately after the training session produced significant memory impairment in the mouse passive avoidance performance. Interestingly, this memory impairment was alleviated by subcutaneous administrations of sigma receptor agonists, (+)-N-allylnormetazocine ((+)-SKF-10,047), (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP) and 1,3-di(2-tolyl)guanidine (DTG) immediately after the training session. In particular, the remarked recovery for this memory impairment was produced by (+)-SKF-10,047. A receptor binding study showed that CDEP possessed high affinities for both sigma 1 and sigma 2 receptor subtypes (IC50 1.4 +/- 0.3 nM for sigma 1 receptor subtype, 1.8 +/- 0.3 nM for sigma 2 receptor subtype), while (+)-SKF-10,047 had a high selectivity for the sigma 1 receptor subtype. These findings suggest that the sigma receptor, particularly sigma 1 receptor subtype, may play an important role in the CDEP-induced impairment of learning and memory processes.

Protective Effect of GTS-21, a Novel Nicotinic Receptor Agonist, on Delayed Neuronal Death Induced by Ischemia in Gerbils

The neuroprotective effects of GTS-21 [3-(2,4-dimethoxybenzylidene)-anabaseine dihydrochloride] were studied and compared with those of nicotine, 9-amino-1,2,3,4-tetrahydroacridine hydrochloride hydrate (THA) and pentobarbital-Na (PB) using a cerebral ischemia model in Mongolian gerbils. The learning performance and memory retention were elucidated by a step-through passive avoidance task at 2 and 3 days after ischemia-reperfusion. In this task, the ischemia-operated gerbils showed impairment of learning performance and memory retention. Neuronal cell death in the hippocampal CA1 area was observed at 7 days after ischemia. When administered i.p. 30 min before ischemia, GTS-21 (5 mg/kg), (—)-nicotine (1.5 mg/kg), THA (5 mg/kg) and PB (50mg/kg) significantly attenuated the impairment of passive avoidance performance and the neuronal cell death induced by the ischemia. When administered orally twice daily for 2 weeks prior to the ischemia, GTS-21 (10 mg/kg) significantly suppressed both amnesia and neuronal cell death, while (—)-nicotine (10 mg/kg) and THA (10 mg/kg) suppressed only the amnesia. These results suggest that GTS-21 exerts a protective activity on not only impairment of learning and memory but also delayed neuronal death and that the underlying mechanism of GTS-21 differs from that of nicotine or THA.

Indeloxazine hydrochloride improves impairment of passive avoidance performance after fluid percussion brain injury in rats

We studied behavioral and histological changes after fluid percussion brain injury and the effects of indeloxazine hydrochloride, a cerebral activator, on these post-traumatic changes in rats. An acquisition trial in passive avoidance task was conducted on the 3rd day after injury. The latency of step-through in injured rats was significantly ( p < 0.05) shorter than that in sham-operated rats on the 4th, 10th and 14th days after the operation. There were injury-induced neurological deficits on days 1–4 post-injury. Histological changes were observed in the peripheral area of the cortical lesion at the impact site and in the thalamus but not in the hippocampus on the 14th day. Indeloxazine (10 and 20 mg/kg, p.o.) administered once a day from the 3rd (30 min prior to the acquisition trial) to the 9th day after injury significantly ( p < 0.05) improved the impairment of the passive avoidance performance without affecting locomotor activity. Indeloxazine showed no significant effects on either neurological deficits or the cortical lesion area. These results suggest that impairment of passive avoidance performance occurs without apparent histological damage in the hippocampus after fluid percussion brain injury and is attenuated by post-traumatic treatment with indeloxazine.

Impairment of Passive Avoidance Performance in SART-Stressed Mice and the Action of Drugs

In order to investigate the behavioral characteristics of the SART-stressed (repeated cold-stressed) animal, a model of dysautonomia, step-down passive avoidance performance was examined in SART-stressed mice. SART-stressed mice exhibited a shortened test trial latency and a decreased incidence of maximum latency of 300 sec, but no change in the training latency. These alterations were blocked by single administration of chlorpromazine or carpipramine prior to the training trial. Repeated, but not single treatments with neurotropin and hopantenate improved the impaired performance due to SART stress. On the other hand, alprazolam and diazepam were ineffective by either mode of administration. Thus, SART-stressed mice appear to have impairment in the process of acquisition of a passive avoidance task.

Impairment of passive avoidance performance in SART-stressed mice and the action of drugs.

In order to investigate the behavioral characteristics of the SART-stressed (repeated cold-stressed) animal, a model of dysautonomia, step-down passive avoidance performance was examined in SART-stressed mice. SART-stressed mice exhibited a shortened test trial latency and a decreased incidence of maximum latency of 300 sec, but no change in the training latency. These alterations were blocked by single administration of chlorpromazine or carpipramine prior to the training trial. Repeated, but not single treatments with neurotropin and hopantenate improved the impaired performance due to SART stress. On the other hand, alprazolam and diazepam were ineffective by either mode of administration. Thus, SART-stressed mice appear to have impairment in the process of acquisition of a passive avoidance task.

Pervasive hyperactivity and long-term learning impairments in rats with induced micrencephaly from prenatal exposure to methylazoxymethanol

Pregnant Long-Evans rats were given a single i.p. injection of 30 mg/kg of methylazoxymethanol (MAM) acetate or saline on day 14 of gestation (vaginal plug = day 0). All litters were reduced to 8 at birth and were reared by their biological dams. Between 49–192 days of age all offspring were examined on open-field, figure-8 (at two different ages), and hole-board tests of activity, as well as passive avoidance and Biel water maze tests of learning (also at two different ages). The MAM offspring showed no increase in mortality, but weighed less than controls, a difference that remained relatively constant throughout the experiment. At 204–215 days of age the MAM offspring were confirmed to be micrencephalic, a known effect of this drug at this dose and exposure period. On all tests of activity the MAM offspring were markedly hyperactive. The female progeny also exhibited a pronounced impairment of normal activity habituation patterns. The MAM males, however, showed a marked impairment of passive avoidance performance, while the females did not. At 2 months of age the MAM offspring also showed a pronounced deficit in learning a water maze. This maze deficit had not abated when tested again at 6 months of age. The MAM induced brain and behavioral abnormalities provide a potentially useful animal model of congenital micrencephaly and associated mental retardation.