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The interaction between the cholinergic and dopaminergic system in learning and memory process in rats.

In normal rats, muscarinic acetylcholine receptors (mAChRs) have a facilitating role on both short-term and long-term memory tested by Y-maze task and multi-trial passive avoidance test, respectively, since scopolamine, a specific mAChRs antagonist, impairs both types of memory. A low dose of nicotine (0.3 mg/kg b.w., i.p.), a specific nicotinic acetylcholine receptors (nAChRs) agonist, administered once caused a significant facilitating effect on short-term memory. A higher dose of nicotine (3 mg/kg b.w., i.p.) administered 5 consecutively days had about the same facilitating effect on short- and long-term memory without affecting information acquisition. In rats, having mAChRs and nAChRs blocked by means of scopolamine and chlorisondamine respectively, a low dose of nicotine administered once caused a significant improvement of long-term memory deficits without affecting significantly short-term memory. A higher dose of nicotine administered 5 consecutive days in rats with a double blockade of cholinergic receptors had the same ameliorating effect on long-term memory deficits as low dose. Our data suggest that the antiamnesic effect of nicotine can result from an action at nicotinic receptors subtypes not blocked by chlorisondamine or at nonnicotinic receptors.

Animals↗

Clitoria ternatea (Linn) root extract treatment during growth spurt period enhances learning and memory in rats.

Neonatal rat pups (7 days old) were intubated with either 50 mg/kg body weight or 100 mg/kg body weight of aqueous root extract of Clitoria ternatea (CTR) for 30 days. These rats were then subjected to open field, two compartment passive avoidance and spatial learning (T-Maze) tests (i) immediately after the treatment and (ii) 30 days after the treatment, along with age matched normal and saline control rats. Results showed no change in open field behaviour, but showed improved retention and spatial learning performance at both time points of behavioural tests, indicating the memory enhancing property of CTR which implicates a permanent change in the brain of CTR treated rats.

Animals↗

Tamoxifen and toremifene cause impairment of learning and memory function in mice.

Tamoxifen (TAM) and toremifene (TOR) are two antiestrogen agents frequently used in the treatment of breast cancer. They are currently being assessed as the prophylactic for patients at high risk of developing tumors. However, the side effects of these drugs on memory function have drawn attention in clinical usage. In the present study, it is demonstrated in mice that TAM and TOR significantly shortened the escaping latency or increased the number of errors, respectively, by using the step-down and step-through passive avoidance tests. By using an appetitively motivated task in T-maze, it is demonstrated that TAM and TOR significantly delayed the latency of finding food in well-trained mice. TAM appeared to impair memory consolidation and retrieval processes, rather than acquisition of memory, whereas TOR appeared to impair acquisition, consolidation, and retrieval processes. These results provide experimental support for the clinical findings that have shown that these drugs impaired memory function in patients routinely taking the drugs and suggest that caution should be taken for using these drugs as the prophylactics for those at risk of developing tumors.

Animals↗

[Participation of the genetic apparatus of the hippocampal and neocortical cells in the mechanisms of action of desglycine-arginine vasopressin on learning and memory processes in rats].

The paper deals with the influence of synthetic vasopressin analogue--desglycine-arginine vasopressin (DG-AVP) on the content of RNA and fractional composition of chromatin proteins in the tissue of neocortex and hippocampus of intact white rats and after establishing of two-way avoidance reflex. Administration of the peptide alone significantly increased RNA content in hippocampal tissue, injection of the peptide 10 min before conditioning did not lead to significant changes in RNA quantity as compared to that in animals in which the conditioned reflex was established against the background of saline administration. In neocortical tissue neither learning itself nor administration of DG-AVP alone was accompanied by significant changes in RNA content, while learning against the background of peptide injection significantly increased RNA in that structure. In hippocampal and neocortical tissues quantitative changes were observed in certain fractions of chromatin proteins in all animal groups studied.

Animals↗

Long-term potentiation: a good model for learning and memory?

1. Long-term potentiation (LTP), long-term depression (LTD), and depotentiation of synaptic activity have been suggested to model synaptic plastic changes that occur during learning. Recent reports however show that neither LTP induced by high frequency stimulation (HFS) in the dentate, CA3, or CA1, nor depotentiation in area CA1 of the hippocampus, are reliable models of the learning abilities of rats or mice. LTD cannot reliably be obtained in the hippocampus in vivo and might be an artefact caused by altered inhibitory transmission. 2. Experiments with gene deletion ('knock out') mice strains show that mice that do not express HFS-induced LTP in the dentate are able to learn spatial tasks. 3. Studies of the effect of NMDA receptor blockers also showed that HFS-induced LTP in the dentate is not a model for processes that occur during learning. Studies using drugs that act on metabotropic glutamate receptors showed that HFS-induced LTP or depotentiation of LTP in area CA1 are not models for learning mechanisms either. 4. Neither in vivo recording of naturally-occurring LTP in the dentate nor synaptic saturation experiments in the hippocampus was able to support the theory that LTP occurs during learning. 5. While in vitro experiments are essential tools to investigate cellular and subcellular mechanisms that underlay synaptic transmission, measurements of LTP, LTD, or DP are not reliable models for learning processes and cannot replace experiments with intact animals that learn spatial tasks.

Animals↗

Effect of a new anxiolytic, DN-2327, on learning and memory in rats.

The effects of a new anxiolytic, (2-(7-chloro-1,8-naphthyridin-2-yl)-3- [(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-carbonylmethyl] isoindolin-1-one (DN-2327), on the execution of step-through passive avoidance and delayed spontaneous alternation tasks were assessed and compared with those of diazepam (DZP) and buspirone. DN-2327 and buspirone (both 10 and 20 mg/kg, PO) impaired performance in the 48-h passive avoidance recall test when given prior to the test session, but not when given before the training trial. DZP impaired the performance at doses of more than 5 and more than 10 mg/kg PO when given prior to the test session and when given before the training trial, respectively. The action of DZP (10 mg/kg PO) when given before the training trial was antagonized by flumazenil (20 mg/kg, IP) and tended to be antagonized by DN-2327 (10 and 30 mg/kg, PO), but was not affected by buspirone. No evidence for possible amnesic effects of DN-2327 or buspirone on working memory was found in the delayed spontaneous alternation task, but DZP (3 and 10 mg/kg, PO) caused significant impairment of working memory. Electroshock sensitivities detected by flinch, jump, and vocalization thresholds were not influenced significantly by DN-2327 (30 and 100 mg/kg, PO), DZP (10 and 30 mg/kg, PO) or buspirone (30 and 100 mg/kg, PO).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

2R,4R-APDC influence on hypoxia-induced impairment of learning and memory processes in passive avoidance test.

We investigated the effects of 2R,4R-APDC, a selective group II metabotropic glutamate receptor (II mGluR) agonist, on certain behaviors in rats subjected and non-subjected to hypoxia. Short-term hypoxia was used as a model of experimentally induced amnesia. 2R,4R-APDC given intracerebroventricularly (icv) at doses of 1 mumol and 100 nmol decreased the number of crossings and rearings in the open field, impaired acquisition and consolidation but improved retrieval in the passive avoidance tests. It also shortened the time spent in open arms and prolonged the time spent in closed arms, reduced the number of open and closed arms entries in an elevated "plus" maze, which is a measure of anxiety. Four-minute hypoxia (2% O(2), 98% N(2)) retrieval of conditioned responses, and exhibited an anxiogenic effect in the elevated "plus" maze in rats, i.e. it reduced the time spent in open arms and the number of entries to closed and open arms. 2R,4R-APDC effect on locomotor and exploratory activity was not changed after hypoxia, i.e. we observed inhibition of motility. This agonist of II mGluRs used at both doses before hypoxia significantly improved acquisition and retrieval, and had dual effect on consolidation, viz. at a dose of 1 mumol, it impaired this process and at a dose of 100 nmol it improved it. In the elevated "plus" maze, rats pretreated with 2R,4R-APDC and then subjected to hypoxia shortened the time spent in open arms and prolonged the time spent in closed arms, reduced the time spent in open arms, i.e. the drug exhibited anxiogenic effect. We conclude, therefore, that 2R,4R-APDC itself impaired acquisition and consolidation, enhanced retrieval but in rats undergoing hypoxia, it improved acquisition, retrieval and when used at the dose of 100 nmol enhanced consolidation. 2R,4R-APDC had beneficial effect in hypoxia-induced memory impairment in passive avoidance test.

Animals↗

Age differences in learning and memory on a digit-symbol substitution task.

Fifteen young (18 to 28 years) and fifteen old (65 to 75 years) persons were given ten 30-second trials on a modified Digit-Symbol task. Both immediate and delayed (24-hour) recall and recognition measures were used to determine how well they remembered the digit-symbol pairs. Both age groups showed similar, significantly improvement over the 10 trials, although the performance level of the young group was higher throughout. The young group showed significantly higher recall and recognition (both immediate and delayed) for the digit-symbol pairs and were more likely to report the use of mnemonic techniques in learning the pairs.

Adolescent↗

Impairment of learning and memory in shuttle box-trained rats neonatally injected with 6-hydroxydopamine. Effects of nootropic drugs.

The effect of neonatal 6-hydroxydopamine (6-OHDA) treatment on learning and retention and on the level of biogenic monoamines in some brain structures as well as the influence of the nootropic drugs--piracetam, aniracetam, meclofenoxate and fipexide on the 6-OHDA-induced effect was studied. Two- way active avoidance (shuttle box) was used. The levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the frontal cortex, striatum, hypothalamus, hippocampus and pons were measured. In mature rats, injected with 6-OHDA (100 mg/kg s.c.) in the first 3 postnatal days learning and retention were impaired and the NA level in the frontal cortex and hippocampus was decreased. Piracetam (600 mg/kg), aniracetam (50 mg/kg), meclofenoxate (100 mg/kg) and fipexide (10 mg/kg) administered orally 5 days before and 5 days during training, abolished the amnestic effect of 6-OHDA and restored to control values the NA level in the frontal cortex and hippocampus. This finding suggests the important role of the noradrenergic neurotransmitter system in the 6-OHDA-induced amnesia, as well as in the favorable effect of the nootropic drugs tested on 6-OHDA-impaired memory processes.

Animals↗

Attenuation by a sigma1 (sigma1) receptor agonist of the learning and memory deficits induced by a prenatal restraint stress in juvenile rats.

1. Stress during pregnancy results in complex neurochemical and behavioral alterations throughout the offspring lifetime. We here examined the impact of prenatal stress (PS) on memory functions in male and female offspring and report the efficacy of a selective sigma(1) (sigma(1)) receptor agonist, igmesine, in alleviating the observed deficits. 2. Dams received an unpredictable 90-min duration restraint stress from gestational day E17 to E20. Learning was examined in offspring between day P24 and P36 using spontaneous alternation in the Y-maze, delayed alternation in the T-maze, water-maze learning and passive avoidance. 3. Both male and female PS rats showed impairments of spontaneous and delayed alternation performances. Acquisition of a fixed platform position in the water-maze was unchanged in PS rats, but the probe test revealed a diminution of time spent in the training quadrant. Acquisition of a daily changing platform position demonstrated impaired working memory for male and female PS rats. Finally, passive avoidance deficits were observed. 4. Pretreatment with the selective sigma(1) agonist igmesine (1-10 mg x kg(-1) i.p.) reversed the PS-induced learning deficits in offspring rats for each test. The sigma(1) antagonist BD1063 failed to affect performances alone but blocked the igmesine effect, confirming the involvement of the sigma(1) receptor. 5. PS thus induces delayed memory deficits, affecting spatial and nonspatial, short- and long-term memories in juvenile male and female offspring rats. Activation of the sigma(1) neuromodulatory receptor allows a significant recovery of the memory functions in PS rats.

Animals↗

Behavioral and neurochemical sequelae in young rats of antenal hypoxia.

To test the hypothesis that perinatal hypoxia may have postnatal consequences via à vis learning memory, and neurochemical sequelae, we exposed pregnant Sprague-Dawley rats to 10.5% O2 for 4 h per day (0800-1200 h) or continuously from gestional day E15 to E20. On E20 we quantified ornithine decarboxylase activity and polyamine concentrations in fetal brain. We also conducted behavioral tests from postnatal day P3 to P110. Relatively mild antenatal hypoxia resulted in altered learning, memory, and delayed maturation of early developmental sensorimotor function. These behavioral changes disappeared at various postnatal ages, depending on the function. Perinatal hypoxia also altered the pharmacological response to dopaminergic drugs. In addition, antenatal hypoxia feminized a male nonreproductive sexual behavior, that of saccharin preference. Acute hypoxia also resulted in an increase in the enzyme ornithine decarboxylase and polyamines, which may affect brain development.

Animals↗

Right hemisphere mediation of verbal learning and memory in acquired right hemisphere speech dominant patients.

Forty-eight patients with temporal lobe epilepsy completed measures of narrative recall and list learning prior to surgery. The intracarotid amytal procedure (IAP) established that 13 patients were right hemisphere dominant for speech and 35 (18 left foci, 17 right foci) were left hemisphere dominant. Hippocampal volumetric neuron densities were measured after surgery. The left hippocampal neuron densities in subfields CA3 and the hilar area were significantly correlated with list learning ability and percent retention for narrative recall only for left hemisphere speech dominant patients with left seizure foci. No significant correlations between measures of neuron volume and memory were found for the left hemisphere speech dominant patients with right seizure foci or the right hemisphere speech dominant patients with left seizure foci. This suggests that the right hemisphere of right speech dominant patients mediates verbal memory as well as speech. This conclusion is supported by patterns of correlations among measures of verbal memory that differed for patients undergoing resection of the dominant hemisphere versus those undergoing resection of the nondominant hemisphere. However, it is premature to conclude that the cerebral organization of cognitive functions of right hemisphere speech dominant patients is equivalent albeit reversed from that of left hemisphere speech dominant patients. Right hemisphere speech dominant patients with left temporal foci differed from left hemisphere speech dominant patients with right temporal foci with respect to the patterns of correlations between measures of verbal memory and intelligence as well as the level of intellectual ability that they demonstrated.

Adult↗

Regional cerebral volume loss associated with verbal learning and memory in dementia of the Alzheimer type.

Twenty-seven research participants with dementia of the Alzheimer type were studied with the California Verbal Learning Test (D. C. Delis, J. H. Kramer, E. Kaplan, & B. A. Ober, 1987) and standardized volume measures of the mesial temporal cortical gray matter, neocortical gray matter, thalamus, and caudate nuclei, from magnetic resonance imaging. A pattern of atrophic brain changes in the mesial temporal lobes (MTL) and the thalamus, with relatively less severe atrophy in the neocortical gray matter, was associated with poorer learning of the word list. Similar patterns of brain atrophy were observed for measures of delayed recall and recognition hits. However, for delayed recall, neither contribution was statistically significant, and for recognition hits, MTL was only at the trend level for significance. These results provide evidence that the verbal memory deficit of Alzheimer's disease (AD) is associated not only with the mesial temporal limbic cortex, thought to be the site of earliest and most severe pathology in AD, but also with damage in the thalamus.

Aged↗