OBJECTIVETo explore the changes in spatial learning performance and long-term potentiation (LTP) which is recognized as a component of the cellular basis of learning and memory in normal and lead-exposed rats after administration of melatonin (MT) for two months.

METHODSExperiment was performed in adult male Wistar rats (12 controls, 12 exposed to melatonin treatment, 10 exposed to lead and 10 exposed to lead and melatonin treatment). The lead-exposed rats received 0.2% lead acetate solution from their birth day while the control rats drank tap water. Melatonin (3 mg/kg) or vehicle was administered to the control and lead-exposed rats from the time of their weaning by gastric gavage each day for 60 days, depending on their groups. At the age of 81-90 days, all the animals were subjected to Morris water maze test and then used for extracellular recording of LTP in the dentate gyrus (DG) area of the hippocampus in vivo.

RESULTSLow dose of melatonin given from weaning for two months impaired LTP in the DG area of hippocampus and induced learning and memory deficit in the control rats. When melatonin was administered over a prolonged period to the lead-exposed rats, it exacerbated LTP impairment, learning and memory deficit induced by lead.

CONCLUSIONMelatonin is not suitable for normal and lead-exposed children.

Animals ; Female ; Lead ; toxicity ; Learning ; drug effects ; Long-Term Potentiation ; drug effects ; Male ; Maze Learning ; drug effects ; Melatonin ; administration & dosage ; toxicity ; Rats ; Spatial Behavior ; drug effects

It is known that stimulation of the α(2A)-adrenoceptors (α(2A)-ARs) by the selective α(2A)-AR agonist guanfacine produces an important and beneficial influence on prefrontal cortical (PFC) cognitive functions such as spatial working memory and selective attention. However, it is unclear whether stimulation of the α(2A)-ARs has a similar effect on fear conditioning that involves the amygdala and hippocampus. Here, we show that systemically administered guanfacine significantly enhances spatial learning of rats in the Lashley maze: compared with controls, the rats treated with guanfacine required significantly fewer trials and made significantly fewer errors to reach learning criterion. However, guanfacine produced no effect on acquisition of contextual and auditory fear memories. The present study suggests that beneficial effect of α(2A)-AR stimulation is task-dependent: guanfacine improves spatial learning but not fear conditioning.
Adrenergic alpha-2 Receptor Agonists ; pharmacology ; Animals ; Behavior, Animal ; drug effects ; Conditioning (Psychology) ; drug effects ; Fear ; drug effects ; Guanfacine ; pharmacology ; Maze Learning ; drug effects ; Memory ; drug effects ; Rats ; Spatial Behavior ; drug effects

This study was designed to examine the effects of recombinant human growth hormone replacement on somatic growth and cognitive function in hypophysectomized (HYPOX) female Sprague-Dawley rats. Rats (5 per group) were randomized by weight to 3 experimental groups: group 1, administered 200 microgram/kg of GH once daily for 9 days; group 2, administered 200 microgram/kg of GH twice daily; and group 3, administered saline daily. Somatic growth was evaluated by measurement of body weight daily and of the width of the proximal tibial growth plate of the HYPOX rats. Cognitive function was evaluated using the Morris water maze (MWM) test. The results indicated that GH replacement therapy in HYPOX rats promoted an increase in the body weight and the width of the tibial growth plate in a dose-dependent manner. On the third day of the MWM test, the escape latency in the GH-treated groups 1 and 2 was significantly shorter than that in the control rats (P<0.001 and P=0.032, respectively), suggesting that rhGH improved spatial memory acquisition in the MWM test. Therefore it is concluded that rhGH replacement therapy in HYPOX rats stimulates an increase in somatic growth in a dose-dependent manner and also has beneficial effects on cognitive functions.
Animals ; Body Weight ; Female ; Growth/*drug effects ; Growth Plate/drug effects/pathology ; Human Growth Hormone/administration & dosage/*pharmacology ; Humans ; *Hypophysectomy ; Rats ; Rats, Sprague-Dawley ; Spatial Behavior/*drug effects

OBJECTIVE: To study the effects of ketamine and alcohol on learning and memory in mice and its possible mechanism. METHODS: Forty mice were divided into 4 groups: normal control group, ketamine group, alcohol group, and alcohol plus ketamine group. Ketamine and alcohol were given by intraperitoneal injection and intragastric administration, respectively, 1 time per day, for 14 days. The ability of learning and memory in mice was tested by the method of step-down and Morris water maze. Acetylcholine (ACh) and 5-hydroxy tryptamine(5-HT) in mice brain tissue were analyzed for the possible mechanism. RESULTS: (1) Step-down: The treatment groups lessened the latency and added wrong times (P < 0.05). The number of errors in the combined treatment group significantly increased comparing with the single drug treatment group (P < 0.05). (2) Morris water-maze: The treatment groups prolonged the latency (P < 0.05), reduced the target quadrant activity time significantly (P < 0.05), and decreased the numbers of crossing the former platform significantly (P < 0.05). (3) Biochemical index determination: The concentrations of ACh and 5-HT in treatment groups decreased significantly (P < 0.05), showed a more decreasement comparing with the single drug treatment group. CONCLUSION Ketamine has a synergistic effect with alcohol on learning and memory impairment in mice, which may be related to the common inhibitive effect on the ACh and 5-HT.
Acetylcholine/metabolism* ; Alcohols/pharmacology* ; Animals ; Brain/physiopathology* ; Drug Synergism ; Ketamine/pharmacology* ; Male ; Maze Learning/drug effects* ; Memory/drug effects* ; Memory Disorders/physiopathology* ; Mice ; Mice, Inbred ICR ; Serotonin/metabolism* ; Spatial Behavior/drug effects*

OBJECTIVETo investigate the effects of citicoline on spatial learning and memory of rats after focal cerebral ischemia.

METHODSThe rats were randomly divided into sham-operation group, ischemia control group and citicoline group. In the later two groups, focal cerebral ischemia model was established by introducing an intraluminal filament into the left middle cerebral artery, and citicoline (500 mg/kg) or 0.9% NaCl was administered intraperitoneally once a day for 2 weeks after the operation. The rats in the sham-operation group were not subjected to middle cerebral artery occlusion (MCAO) with intraluminal filament. The spatial learning and memory functions of the rats were evaluated by Morris water maze test 15 days after MCAO for 5 days.

RESULTSThe rats in ischemia control group exhibited serious spatial learning and memory deficits in both place navigation test and spatial probe test. In the former test, the mean escape latency of citicoline-treated rats were significantly shorter than that of ischemia control rats (P<0.01), and in the latter test significant diffidence was noted between citicoline and ischemia control groups in the percentage time spent in the former platform quadrant and frequency of crossing the former platform (P<0.05).

CONCLUSIONCiticoline can improve the spatial learning and memory function of rats after focal cerebral ischemia.

Animals ; Avoidance Learning ; drug effects ; Cytidine Diphosphate Choline ; pharmacology ; Infarction, Middle Cerebral Artery ; physiopathology ; Male ; Maze Learning ; drug effects ; Nootropic Agents ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spatial Behavior ; drug effects

OBJECTIVETo investigate the effect of GEPT extracts on spatial learning ability of the APPV717I transgenic mice at the early stage of dementia and its possible mechanism.

METHODThirty APPV717I transgenic mice were randomly divided into three GEPT groups by intragastric administration at doses of 0.075, 0.15, 0.3 g x kg(-1) x d(-1), and a donepezil group by intragastric administration of 0.92 mg x kg(-1) x d(-1), a APPV717I transgenic model group and a normal group by intragastric administration of distilled water. A four-month treatment regimen with GEPT extracts was administered to APPV717I transgenic mice. Results showed that Spatial memory ability was measured in Morris water maze. The total area covered by shank1 and integral optical density in CA1 subfield within the hippocampus were determined using immunohistochemical stains and Image-Pro plus analysis. The ultrastructure of synapses in the hippocampal CA1 region was observed by electronic microscope.

RESULTAfter a four-month of GEPT treatment regimen, the mean escape latency period were significantly shortened (P < 0.05), and the target quadrant search time were significantly increased (P < 0.05) compared to the APPV717I transgenic model mice. There was a significant higher level in the expression of shank1 detected in the hippocampal CA1 area of APPV717I transgenic mice associated with an increase in the number of synapses treated with GEPT than the levels in the APPV717I transgenic model mice alone. The total area of positive cells covered by shank1 and their integral optical density in the hippocampal CA1 area of the APPV717I transgenic mice treated with GEPT were significantly increased more than those of the APPV717I transgenic model mice.

CONCLUSIONGEPT extracts can obviously improve the spatial memory ability of APPV717I transgenic mice at the early stage of dementia through enhancing the number of synapses and the expression of shank1, and this might lead to development of novel treatment therapies for the memory loss associated with AD.

Animals ; Dementia ; prevention & control ; Disease Models, Animal ; Female ; Learning ; Male ; Memory ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Panax ; chemistry ; Plant Extracts ; therapeutic use ; Space Perception ; drug effects ; physiology ; Spatial Behavior ; drug effects ; physiology

OBJECTIVETo observe the therapeutic effect of Yangxue Qingnao Granule (, YXQNG) on cognitive impairment induced by chronic cerebral hypoperfusion and to investigate its impact on oxidative stress, apoptosis, and the cholinergic system.

METHODSAdult male Wistar rats were subjected to chronic cerebral hypoperfusion by permanent occlusion of bilateral common carotid arteries (2-VO). Thirty rats were randomly assigned to one of the five treatment groups in a 1:1:1:1:1 ratio: sham operation plus normal saline treatment, 2-VO plus normal saline treatment, 2-VO plus YXQNG at a dose of 2 g·kg(-1)·d(-1) or 4 g·kg(-1)·d(-1), or 2-VO plus rivastigmine 2 mg·kg(-1)·d(-1). The Morris water maze test was used to assess the spatial memory retrieval. Apoptosis, total antioxide capacity (T-AOC), acetylcholine esterase (AchE) and choline acetyl transferase (ChAT) activities in the hippocampus and the cortex were investigated.

RESULTSIn the chronic cerebral hypoperfusion model, the 2-VO plus saline treatment resulted in impaired special learning as shown by the significantly prolonged escape latency and shorter swim time in the first quadrant as compared to the sham operation. The impairment was associated with apoptosis and significant decreases in T-AOC, AchE and ChAT activities in the hippocampus and the cortex. Treatment with YXQNG at either 2 g·kg(-1)·d(-1) or 4 g·kg(-1)·d(-1) dose, or rivastigmine resulted in significantly shorter escape latencies and longer swim time in the first quadrant. YXQNG at both doses, but not rivastigmine, had significant reduction in apoptosis, and significant increases in T-AOC and ChAT activity in both the hippocampus and the cortex. Unlike rivastigmine, neither dose of YXQNG showed significant reduction in AchE activity.

CONCLUSIONSYXQNG ameliorated cognitive impairment induced by chronic cerebral hypoperfusion. The protective effect may be mediated through its regulation of apoptosis and activities of T-AOC and ChAT in the hippocampus and cortex of the rats in the chronic cerebral hypoperfusion model, a mechanism that is different from rivastigmine.

Animals ; Apoptosis ; drug effects ; Brain ; drug effects ; pathology ; Chemistry, Pharmaceutical ; Chronic Disease ; Cognition Disorders ; drug therapy ; etiology ; pathology ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Hypoxia-Ischemia, Brain ; complications ; drug therapy ; pathology ; Male ; Maze Learning ; drug effects ; Rats ; Rats, Wistar ; Spatial Behavior ; drug effects ; Task Performance and Analysis

OBJECTIVETo study the effects of Bushen Yin' ao Tablet (BSYNT) on physiology and cerebral gene expression in senescence-accelerated mice (SAM).

METHODSThe change of cerebral tissues mRNA expression in SAM was analyzed and compared by messenger ribonucleic acids reverse transcription differential display polymerase chain reaction (mRNA DDRT-PCR) between the medicated group and the control group.

RESULTSBSYNT could increase the level of hemoglobin (Hb) and amount of erythrocyte (RBC) of blood deficiency mice, improve the spatial learning and memory function and the escape response by conditional stimulus. In this study, 14 differential display bands had been discerned, and three of them had been sequenced. The sequence of the three fragments was similar to fatty acid binding protein 7, ubiquinol-cytochrome C reductase complex (7. 2 kD) and 60S ribosomal protein L21 respectively. And the homogeneity was 97% , 100% , and 99% , respectively.

CONCLUSIONBSYNT has effect on the physiological changing of mice, and its effect on cerebral tissues mRNA expression maybe play an important role in anti-aging on the molecular level.

Aging ; drug effects ; Animals ; Brain ; drug effects ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Electron Transport Complex III ; genetics ; metabolism ; Erythrocyte Count ; Fatty Acid-Binding Protein 7 ; Fatty Acid-Binding Proteins ; genetics ; metabolism ; Gene Expression ; drug effects ; Hemoglobins ; metabolism ; Mice ; Nerve Tissue Proteins ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Ribosomal Proteins ; genetics ; metabolism ; Spatial Behavior ; drug effects ; Tablets

OBJECTIVETo investigate the effect and possible mechanism of complete Freund's adjuvant induced chronic pain on later function of learning and memory in neonatal rats.

METHODSSixty Sprague-Dewley rat pups (10 litters of 6 pups) were randomly divided into control group and chronic pain group (n = 30 in each group). In the chronic pain group, left hind paws of the rats were treated with subcutaneous injection of 20 microl of CFA on postnatal day-2. The control rat pups received normal saline. The hippocampus of rats were separated on postnatal days 10 and 21 (one rat in each group from every litter, n = 10). The expression of Bcl-2 and BDNF mRNA were investigated by RT-PCR. Morris water maze tests were performed on day 21 (one rat in each group from every litter, n = 10).

RESULTSIn hidden-platform training of Morris water maze, the mean escape latency of rats in the chronic pain group were longer than that of the control rats. In spatial probe tests, the average percentages of the swimming time and distances in the platform quadrant in the pain group rats were less than those in the control group. There was no significant difference in visible-platform training between the two groups. The Bcl-2 and BDNF mRNA expressions in hippocampus of the pain group rats were lower than those in the control at day 10, but no significant difference at day 21.

CONCLUSIONChronic pain stress induced by CFA impairs the spatial learning and memory function in neonatal rats. These effects might exert through down-regulating Bcl-2 and BDNF mRNA expression in the hippocampus.

Animals ; Animals, Newborn ; Brain-Derived Neurotrophic Factor ; genetics ; Chronic Disease ; Disease Models, Animal ; Down-Regulation ; Freund's Adjuvant ; Genes, bcl-2 ; genetics ; Hippocampus ; metabolism ; physiopathology ; Maze Learning ; drug effects ; Memory ; drug effects ; Pain ; chemically induced ; genetics ; physiopathology ; psychology ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Spatial Behavior ; Stress, Physiological ; genetics