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PubMedDate not supplied

Effects of concomitant cholinergic and adrenergic stimulation on learning and memory performance by young and aged monkeys.

The beneficial effects of physostigmine and other centrally acting AChE inhibitors on learning and memory processes have been documented in several studies. Some of these compounds are currently being examined for their potential in the treatment of Alzheimer's disease. However, the ability to employ this class of agents alone is limited by the potential for debilitating and dangerous side effects. In addition, a growing body of evidence also suggests a role for a number of other transmitter systems in this disorder. Agents such as clonidine that address adrenergic deficits have recently been demonstrated to enhance memory performance in monkeys. Clonidine also inhibits the function of cholinergic neurons in specific brain regions and reduces certain side effects of physostigmine. This evidence provided the impetus to evaluate a combination of physostigmine and clonidine in a learning and memory paradigm in monkeys. Seven young adult and three aged macaque monkeys performing a delayed matching-to-sample task received regimens of increasing doses of clonidine and physostigmine on separate occasions to determine the optimal dose of each agent in terms of enhanced memory performance. The optimal dose of clonidine was combined with a series of physostigmine doses and performance was compared to that using the two drugs alone. The best combination regimen of clonidine and physostigmine was more effective than either drug alone in enhancing memory performance. Part of the benefit may have been due to the ability of the animals to tolerate significantly higher doses of physostigmine in the combination regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1999

Nociceptin/orphanin FQ and nocistatin on learning and memory impairment induced by scopolamine in mice.

1. Nociceptin, also known as orphanin FQ, is an endogenous ligand for the orphan opioid receptor-like receptor 1 (ORL1) and involves in various functions in the central nervous system (CNS). On the other hand, nocistatin is recently isolated from the same precursor as nociceptin and blocks nociceptin-induced allodynia and hyperalgesia. 2. Although ORL1 receptors which display a high degree of sequence homology with classical opioid receptors are abundant in the hippocampus, little is known regarding their role in learning and memory. 3. The present study was designed to investigate whether nociceptin/orphanin FQ and nocistatin could modulate impairment of learning and memory induced by scopolamine, a muscarinic cholinergic receptor antagonist, using spontaneous alternation of Y-maze and step-down type passive avoidance tasks in mice. 4. While nocistatin (0.5-5.0 nmol mouse-1, i.c.v.) administered 30 min before spontaneous alternation performance or the training session of the passive avoidance task, had no effect on spontaneous alternation or passive avoidance behaviours, a lower per cent alternation and shorter median step-down latency in the retention test were obtained in nociceptin (1.5 and/or 5.0 nmol mouse-1, i.c.v.)-treated normal mice. 5. Administration of nocistatin (1.5 and/or 5.0 nmol mouse-1, i.c.v.) 30 min before spontaneous alternation performance or the training session of the passive avoidance task, attenuated the scopolamine-induced impairment of spontaneous alternation and passive avoidance behaviours. 6. These results indicated that nocistatin, a new biologically active peptide, ameliorates impairments of spontaneous alternation and passive avoidance induced by scopolamine, and suggested that these peptides play opposite roles in learning and memory.

Animals↗
PubMed2000

[Studies on learning and memory function-related genes in the hippocampus and the relationship between the cognitive enhancing effect of liuwei dihuang decoction (LW) and gene expression].

Our studies showed that the expressions of the genes including glucocorticoid receptor (GR), mineralocorticoid receptor (MR), bcl-2, c-fos, neural cell adhesion molecule(NCAM), presenilin-2 (PS-2) and apoE in the hippocampus were closely related to the central learning and memory function in senescence accelerated mice (SAM), hydrocortisone(HC)-treated mice and normal mice. The differential display technique was applied to compare mRNAs expression between SAM-prone/8 (SAMP8), and SAM-resistance/1 (SAMR1). Six differentially expressed cDNA bands were identified and two of them are unknown genes. Chronic oral administration of LW (5 g/kg), a traditional Chinese medicinal prescription, significantly ameliorated the deterioration of learning and memory ability in SAMP8 and HC-treated mice and corrected the abnormal expressions of hippocampal genes. Further studies showed that corticosterone significantly affected the gene expression in primary cultured hippocampal neurons. These results suggested that central learning and memory function is closely related to the expressions of hippocampal genes. The imbalance of hypothalamic-pituitary-adrenal (HPA) axis leads to the deterioration of learning and memory function and the abnormal expressions of hippocampal genes. Therefore, one of the important ways of the cognitive enhancing effect of LW is to correct the abnormal expressions of hippocampal genes.

Aging↗
PubMed2004

The simultaneous acquisition effect: simultaneous task learning inhibits memory for order.

Delayed recall of a list of words learned simultaneously with other lists is superior to that of a list of words learned singly. A Brown-Peterson-like task was used to investigate this simultaneous acquisition effect from the perspective of the item-order distinction. It was hypothesized that simultaneous task learning would impede the encoding of order information but promote the encoding of item-specific information relative to single-task learning. The results of the first four experiments strongly supported the hypothesis that simultaneous task learning decreases the encoding of order information but provided no evidence that it facilitated the encoding of item-specific information. Additionally, Experiment 5 showed that the simultaneous acquisition effect did not occur in a mixed-list design, demonstrating an important boundary condition of the effect.

Humans↗
PubMed2001

Excitotoxic lesions of the rostral thalamic reticular nucleus do not affect the performance of spatial learning and memory tasks in the rat.

Rats with cytotoxic lesions of the rostral pole of the thalamic reticular nucleus were compared with surgical control animals on a series of spatial learning and memory tests. While evidence was found for an initial, transient impairment on forced-choice alternation in a T-maze, this rapidly disappeared, and overall performance was unaffected. Subsequent experiments found no evidence that lesions of the rostral reticular nucleus affected the acquisition or performance of tests in the radial arm maze and the Morris water maze. Thus, it appears that the rostral pole of the thalamic reticular nucleus often does not play a necessary role in the performance of tests of spatial learning and memory, in spite of its interconnections with other regions that are required for normal spatial memory.

Animals↗
PubMed2001

Chronic psychosocial stress impairs learning and memory and increases sensitivity to yohimbine in adult rats.

BACKGROUND: It is well known that intense and prolonged stress can produce cognitive impairments and hippocampal damage and increase noradrenergic activity in humans. This study investigated the hypothesis that chronic psychosocial stress would affect behavior, drug sensitivity, and hippocampal-dependent learning and memory in rats. The work provides a novel connection between animal and human studies by evaluating the effects of stress on a rat's response to yohimbine, an alpha(2) adrenergic receptor antagonist. METHODS: Rats were exposed to a cat for 5 weeks and randomly housed with a different group of cohorts each day (psychosocial stress). The effects of the stress manipulations were then assessed on open field behavior, spatial learning and memory in the radial arm water maze and the behavioral response to a low dose of yohimbine (1.5 mg/kg). RESULTS: Stressed rats displayed impaired habituation to a novel environment, heightened anxiety, and increased sensitivity to yohimbine. In addition, the stressed rats exhibited impaired learning and memory. CONCLUSIONS: There are commonalities between the current findings on stressed rats and from studies on traumatized people. Thus, psychosocial stress manipulations in rats may yield insight into the basis of cognitive and neuroendocrine disturbances that commonly occur in people with anxiety disorders.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed2001

Applications of the Morris water maze in the study of learning and memory.

The Morris water maze (MWM) was described 20 years ago as a device to investigate spatial learning and memory in laboratory rats. In the meanwhile, it has become one of the most frequently used laboratory tools in behavioral neuroscience. Many methodological variations of the MWM task have been and are being used by research groups in many different applications. However, researchers have become increasingly aware that MWM performance is influenced by factors such as apparatus or training procedure as well as by the characteristics of the experimental animals (sex, species/strain, age, nutritional state, exposure to stress or infection). Lesions in distinct brain regions like hippocampus, striatum, basal forebrain, cerebellum and cerebral cortex were shown to impair MWM performance, but disconnecting rather than destroying brain regions relevant for spatial learning may impair MWM performance as well. Spatial learning in general and MWM performance in particular appear to depend upon the coordinated action of different brain regions and neurotransmitter systems constituting a functionally integrated neural network. Finally, the MWM task has often been used in the validation of rodent models for neurocognitive disorders and the evaluation of possible neurocognitive treatments. Through its many applications, MWM testing gained a position at the very core of contemporary neuroscience research.

Animals↗
PubMed1998

Propentofylline improves learning and memory deficits in rats induced by beta-amyloid protein-(1-40).

We have reported that continuous infusion of beta-amyloid protein-(1-40) into the cerebral ventricle produces learning and memory deficits in rats. Propentofylline has potent stimulatory effects on nerve growth factor (NGF) synthesis/secretion in mouse astrocytes in vitro and increases cerebral NGF content in aged rats. In the present study, we examined the effects of propentofylline on learning and memory deficits in beta-amyloid protein-infused rats. The rats were given propentofylline orally once a day throughout the period of behavioral examination. In the beta-amyloid protein-infused rats, spontaneous alternation behavior in a Y-maze, and performance in water maze and passive avoidance tasks were significantly impaired compared to sham-operated rats. Propentofylline prevented these behavioral deficits, but did not change the reduction of the activity of choline acetyltransferase in the hippocampus in the beta-amyloid protein-infused rats. These results suggest that propentofylline is useful for the treatment of patients with Alzheimer's disease.

Administration, Oral↗
PubMed2006

Nardostachys jatamansi improves learning and memory in mice.

Cure of cognitive disorders such as amnesia, attention deficit, and Alzheimer's disease is still far from being realized in the field of medicine. Nootropic agents such as piracetam, aniracetam, and choline esterase inhibitors like donepezil are being used for improving memory, mood, and behavior, but the resulting side effects associated with these agents have made their applicability limited. In Ayurveda, the roots of Nardostachys jatamansi have been clinically employed for their anti-ischemic, antioxidant, anticonvulsant, and neuroprotective activities. The present study was undertaken to assess the potential of N. jatmansi as a memory enhancer. The elevated plus maze and the passive avoidance paradigm were employed to evaluate learning and memory parameters. Three doses (50, 100, and 200 mg/kg, p.o.) of an ethanolic extract of N. jatamansi were administered for 8 successive days to both young and aged mice. The 200 mg/kg dose of N. jatmansi ethanolic extract significantly improved learning and memory in young mice and also reversed the amnesia induced by diazepam (1 mg/kg, i.p.) and scopolamine (0.4 mg/kg, i.p.). Furthermore, it also reversed aging-induced amnesia due to natural aging of mice. As scopolamine-induced amnesia was reversed, it is possible that the memory improvement may be because of facilitation of cholinergic transmission in the brain. Hence, N. jatmansi might prove to be a useful memory restorative agent in the treatment of dementia seen in elderly persons. The underlying mechanism of action can be attributed to its antioxidant property.

Aging↗
PubMed2002

Deterioration in learning and memory of inferential tasks for evaluation of transitivity and symmetry in aged SAMP8 mice.

This study examined age-dependent deficits in the learning and memory of inferential tasks, using an established senescence-accelerated mouse model in age-related brain dysfunction (SAMP8) and its genetically related inbred strain (SAMR1). The mice learned two sets of nonspatial odor-odor pairs by association learning successively (i.e., A-->B, X-->Y, then B-->C, Y-->Z). They were tested in transitive inference (i.e., A-->C, X-->Z) and symmetrical inference (i.e., C-->B, Z-->Y). In the probe test of A-->C, X-->Z transitive inference, 1-month-old SAMP8 and control SAMR1 at the same age significantly chose the alternative based on transitive inference, but 4- and 7-month-old SAMP8 performed at a random chance level, in comparison with unambiguous inference by control SAMR1 at the same ages. During the test of C-->B, Z-->Y symmetrical inference, SAMP8 at 1 month of age made errors as frequently as control SAMR1 at the same age, but SAMP8 at 4 and 7 months of age made more errors than SAMR1 at the same ages. At 4 and 7 months of age, SAMP8 made more errors than 1-month-old SAMP8. Control SAMR1 did not show such an age-related deficient. These results indicate that SAMP8 mice have age-related learning and memory deficits in the ability to perform inferential tasks. Age-related hippocampal dysfunction is suggested to be the cause of these age-related deficits in old SAMP8 mice during the performance of inferential tasks mediated by declarative memory.

Aging↗
PubMed1998

Improvement by FUB 181, a novel histamine H3-receptor antagonist, of learning and memory in the elevated plus-maze test in mice.

Effects of FUB 181 [3-(4-chlorophenyl)propyl-3-(1H-imidazol-4-yl)propyl ether], a novel histamine H3-receptor antagonist, on a scopolamine-induced learning deficit in the elevated plus-maze test were studied in mice. FUB 181 alone (2.5 and 5 mg/kg, i.p.) ameliorated the scopolamine-induced learning deficit in mice. This effect was antagonized by BP 2.94 (10 mg/kg, i.p.), a prodrug of (R)-alpha-methylhistamine (histamine H3-receptor agonist), and by ketotifen (4 mg/kg, i.p.), a histamine H1-receptor antagonist, both penetrating the blood-brain barrier. However, the ameliorating effect of FUB 181 (2.5 mg/kg) was not antagonized by either terfenadine (10 mg/kg, i.p.), a histamine H1-receptor antagonist with poor penetration of the blood-brain barrier, or zolantidine (20 mg/kg, i.p.), a centrally effective histamine H2-receptor antagonist. In a biochemical study, FUB 181 had no significant effect on either acetylcholine or choline level in mice brain at the doses tested. These findings suggest that FUB 181 increases the release of histamine by blocking presynaptic histamine H3 autoreceptors, and that released histamine in turn activates postsynaptic H1 and H2 receptors, predominantly histamine H1 receptors, and in this fashion improves learning and memory in mice. Our findings also suggest that the histaminergic system may play an important role in learning and memory, and that FUB 181 may be a clinical candidate for the therapy of dementia.

Acetylcholine↗
PubMed2006

Rosiglitazone attenuates learning and memory deficits in Tg2576 Alzheimer mice.

The thiazolidinediones, such as rosiglitazone, increase peripheral insulin sensitivity and their use is proposed for the treatment of Alzheimer's disease. However, the mechanisms underlying the potential beneficial effects of rosiglitazone in Alzheimer's disease remain unclear. In previous studies, we observed that Tg2576 Alzheimer mice develop peripheral insulin resistance with age and have much higher serum corticosterone levels than wild-type mice when fasted overnight. We further showed that both of these defects can be ameliorated by rosiglitazone administration. Here, we report that during behavioral testing which involves repetitive overnight fasting, Tg2576 mice administered rosiglitazone exhibited better spatial learning and memory abilities and had lower serum corticosterone levels than untreated Tg2576 mice. When untreated Tg2576 mice were administered metyrapone, a drug that blocks glucocorticoid production, their spatial learning and memory abilities and serum corticosterone levels were similar to those of rosiglitazone-treated mice. We further report here that rosiglitazone attenuated reductions in insulin-degrading enzyme (IDE) mRNA and activity, and reduced amyloid beta-peptide (Abeta)42 levels without affecting amyloid deposition, in the brains of Tg2576 mice. These results demonstrate that rosiglitazone attenuates learning and memory deficits in Tg2576 mice and suggest that the effects of the drug on learning and memory, brain IDE levels, and brain Abeta42 levels in the mice may be due to its glucocorticoid-lowering actions.

Age Factors↗
PubMed2003

Effects of the antidepressant drug moclobemide on learning and memory in rats.

Moclobemide is a well known drug with antidepressant action. The aim of this study was to investigate the effects of moclobemide on learning and memory processes in Sprague Dawley rats. Over a 5-day period, learning sessions with 30 trials per day and memory retention tests were performed. The conditioned responses (avoidances), the unconditioned responses (escapes) and the intertrial crossings were observed. An active avoidance test was carried out using a shuttle box. Two passive avoidance tests were used: step-through (using a light chamber) and step-down (using a platform). In the step-through passive avoidance test, the learning and retention sessions consisted of three trials each and the latency of reaction times (the rat remaining in the light chamber for more than 180 sec) was used as criterion. In the step-down passive avoidance test, learning and retention sessions consisted of two trials and the latency of reaction times (the rat remaining on the platform for 60 sec) was used as criterion. In the active avoidance tests, moclobemide dose-dependently increased the number of avoidances during learning sessions and maintained this number in memory retention tests. Moclobemide did not alter the number of escapes, but did increase motor activity. In the passive avoidance tests, moclobemide also increased the latency of reaction times in learning and short memory retrieval tests. These findings suggest that moclobemide improves learning and memory processes in active and passive avoidance tests and has a cognition-enhancing effect.

Animals↗
PubMed2005

[Behavioral characterization of mouse strains in learning and memory tests].

Here we review the behavioral characterization of several strains of mice that have generally been used in learning and memory tests. We made behavioral comparisons among inbred (C57BL/6, DBA/1 and 129Sv) and closed colony (ddY and ICR (CD-1)) mice. In the water-maze test, the spatial learning ability of C57BL/6 and ICR was higher than that of the other strains of mice. In the Y-maze, water-finding and step-through type passive avoidance tests, there were some differences among those strains but they were not significant. We have to pay attention to the mouse strain to analyze the behavioral changes when we use different strains of mice.

Animals↗
PubMed2006

Involvement of tissue inhibition of metalloproteinases-1 in learning and memory in mice.

Tissue inhibitor of metalloproteinases (TIMP-1) is one of the four-member family (TIMPs-1-4) of multifunctional proteins that inhibit matrix metalloproteinases (MMPs). Its expression in the hippocampus is neuronal-activity-dependent and dramatically induced by stimuli leading to long-term potentiation (LTP), suggesting that TIMP-1 is a candidate plasticity protein potentially involved in learning and memory processes. We tested this hypothesis in a hippocampus-dependent task using the new olfactory tubing maze, with mice carrying a null mutation for TIMP-1 (TIMP-1 KO) and mice overexpressing TIMP-1 (TIMP-1 (tg)). The TIMP-1 KO mice were significantly impaired in making correct odor-reward associations when compared with their respective wild type (WT) littermates, while TIMP-1 overexpressing mice performed better than their WT controls. Both genetically modified mice learned the paradigm and the timing of the task, like their respective WTs, and no olfactory dysfunctioning was observed. These data suggest that TIMP-1 is involved in learning and memory processes related to the hippocampus, and support the hypothesis that the MMP/TIMP ratio, and hence MMP activity, modulates neuronal plasticity in normal learning and memory processes, while altered proteolytic activity could impair cognitive functions.

Animals↗